Review Article
Volume 13 Issue 6 - 2022
Pathogenesis of Elevated Intraocular Pressure and Glaucoma-Related Retinal and Optic Nerve Degeneration: Diverse Mitigation Strategies and Treatment Modalities
Najam A Sharif1-8*
1Department of Surgery and Cancer, Imperial College of Science and Technology, St. Mary’s Campus, London (UK)
2Singapore Eye Research Institute (SERI), Singapore
3SingHealth, Duke-National University of Singapore Medical School, Singapore
4Department of Pharmacology and Neuroscience, University of North Texas Health Sciences Center, Fort Worth, Texas (USA)
5Department of Pharmacy Sciences, Creighton University, Omaha, Nebraska USA)
6Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas (USA)
7Global Alliances and External Research, Ophthalmology Innovation Center, Santen Inc., Emeryville, CA (USA)
8University College London, Institute of Ophthalmology, London (UK)
*Corresponding Author: Najam A Sharif, Ophthalmology Innovation Center, Santen Inc USA, 6401 Hollis St. (Suite 125), Emeryville, CA 94608 (USA).
Received: April 26, 2022; Published: May 31, 2022


Millions of patients bear witness to the devasting effects of the progressive atrophic loss of retinal ganglion cell (RGC) axons within the optic nerve and the subsequent death of RGCs that eventually robs them of their sight due to ocular hypertension (OHT)/ glaucoma. Although a slowly progressing disease, this glaucomatous optic neuropathy (GON) often results from undiagnosed and untreated chronically elevated intraocular pressure (IOP) or OHT. Since many glaucoma patients without OHT also experience visual impairment and eventual blindness, it is now accepted that many pathogenic mechanisms and factors at the front and back of the eye conspire to cause GON. This review addresses such elements of neuroinflammation, aberrant immune responses, oxidative stress, neuronal and nerve terminal retraction and pruning, and RGC apoptosis. Furthermore, it describes means to help overcome the deleterious events connected with OHT and GON ranging from pharmaceutical, nutraceutical, electroceutical, gene-therapy, photoelectric dye and device utilization perspectives.

Keywords: Glaucoma; Ocular Hypertension; Glaucomatous Optic Neuropathy; Drugs; Devices; Therapeutics


  1. Weinreb RN., et al. “The pathophysiology and treatment of glaucoma: a review”. The Journal of the American Medical Association 311 (2014): 1901-1911.
  2. Jonas JB., et al. “Glaucoma”. Lancet 390 (2017): 2183-2193.
  3. Sharif NA. “Ocular hypertension and glaucoma: a review and current perspectives”. International Journal of Ophthalmology and Visual Science 2.3 (2017): 22-36.
  4. Sharif NA. “iDrugs and iDevices discovery and development - preclinical assays, techniques and animal model studies for ocular hypotensives and neuroprotectants”. Journal of Ocular Pharmacology and Therapeutics 34 (2018a): 7-39.
  5. Sharif NA. “Therapeutic drugs and devices for tackling ocular hypertension and glaucoma, and need for neuroprotection and cytoprotective therapies”. Frontiers in Pharmacology 12 (2021): 729249.
  6. Harwerth RS and Quigley HA. “Visual field defects and retinal ganglion cell losses in patients with glaucoma”. Archives of Ophthalmology 124 (2006): 853-859.
  7. Gazzard G., et al. “Intraocular pressure and visual field loss in primary angle closure and primary open angle glaucomas”. British Journal of Ophthalmology 87 (2003): 720-725.
  8. Aung T and Khor CC. “Glaucoma genetics: recent advances and future directions”. The Asia-Pacific Journal of Ophthalmology4 (2016): 256-259.
  9. Berdahl JP., et al. “Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma”. Ophthalmology 115 (2008): 763-768.
  10. Jóhannesson G., et al. “Intracranial and intraocular pressure at the lamina cribrosa: gradient effects”. Current Neurology and Neuroscience Reports5 (2018): 25.
  11. Wostyn P., et al. “Glaucoma and the role of cerebrospinal fluid dynamics”. Investigative Ophthalmology and Visual Science 56 (2015): 6630-6631.
  12. Price DA., et al. “The influence of translaminar pressure gradient and intracranial pressure in glaucoma: a review”. Journal of Glaucoma 292 (2020): 141-146.
  13. Mozaffarieh M., et al. “Oxygen and blood flow: players in the pathogenesis of glaucoma”. Molecular Vision 14 (2008): 224-233.
  14. Pasquale LR. “Vascular and autonomic dysregulation in primary open-angle glaucoma”. Current Opinion in Ophthalmology 27 (2016): 94-101.
  15. Carreon T., et al. “Aqueous outflow - A continuum from trabecular meshwork to episcleral veins”. Progress in Retinal and Eye Research 57 (2017): 108-133.
  16. Sun X., et al. “Primary angle closure glaucoma: What we know and what we don't know”. Progress in Retinal and Eye Research 57 (2017): 26-45.
  17. Chan PP., et al. “Acute primary angle closure-treatment strategies, evidence and economic considerations”. Eye 33 (2019): 110-119.
  18. Tham Y-C., et al. “Global prevalence of glaucoma and projections of glaucoma burden through 2040”. Ophthalmology 121 (2014): 2081-2090.
  19. Blindness and vision impairment- Fact sheets. WHO Priority eye diseases (2019).
  20. Mallick J., et al. “Update on normal tension glaucoma”. Journal of Ophthalmic and Vision Research 11 (2016): 204-208.
  21. Zhang HJ., et al. “Normal tension glaucoma: from the brain to the eye or the inverse?” Neural Regeneration Research11 (2019) :1845-1850.
  22. Civan M and Macknight AD. “The ins and outs of aqueous humor secretion”. Experimental Eye Research 78 (2004): 625-631.
  23. Saccà SC., et al. “Oxidative DNA damage in the human trabecular meshwork: clinical correlation in patients with primary open-angle glaucoma”. Archives of Ophthalmology4 (2005): 458-463.
  24. Izzotti A., et al. “Mitochondrial damage in the trabecular meshwork occurs only in primary open-angle glaucoma and in pseudoexfoliative glaucoma”. PLoS One1 (2011): e14567.
  25. Borrás T. “A single gene connects stiffness in glaucoma and the vascular system”. Experimental Eye Research 158 (2017): 13-22.
  26. Overby DR., et al. “Altered mechanobiology of Schlemm's canal endothelial cells in glaucoma”. Proceedings of the National Academy of Sciences of the United States of America38 (2014): 13876-13881.
  27. Yemanyi F., et al. “Crosslinked extracellular matrix stiffens human trabecular meshwork cells via dysregulating β-catenin and YAP/TAZ signaling pathways”. Investigative Ophthalmology and Visual Science10 (2020): 41.
  28. Tripathi RC., et al. “Aqueous humor in glaucomatous eyes contains an increased level of TGF-beta 2”. Experimental Eye Research6 (1994): 723-727.
  29. Nakamura N., et al. “Effects of topical TGF-β1, TGF-β2, ATX, and LPA on IOP elevation and regulation of the conventional aqueous humor outflow pathway”. Molecular Vision 27 (2021): 61-77.
  30. Von Zee CL., et al. “Transforming growth factor-β2 induces synthesis and secretion of endothelin-1 in human trabecular meshwork cells”. Investigative Ophthalmology and Visual Science 53 (2012): 5279-5286.
  31. Rao VR., et al. “Mitochondrial-targeted antioxidants attenuate TGF-β2 signaling in human trabecular meshwork cells”. Investigative Ophthalmology and Visual Science10 (2019): 3613-3624.
  32. Guo L., et al. “Direct optic nerve sheath (DONS) application of Schwann cells prolongs retinal ganglion cell survival in vivo”. Cell Death and Disease 5 (2014): e1460.
  33. Acott TS., et al. “Normal and glaucomatous outflow regulation”. Progress in Retinal and Eye Research 11 (2020): 100897.
  34. Kasetti RB., et al. “Increased synthesis and deposition of extracellular matrix proteins leads to endoplasmic reticulum stress in the trabecular meshwork”. Scientific Reports1 (2017): 14951.
  35. Kasetti RB., et al. “Expression of mutant myocilin induces abnormal intracellular accumulation of selected extracellular matrix proteins in the trabecular meshwork”. Investigative Ophthalmology and Visual Science14 (2016): 6058-6069.
  36. Bermudez JY., et al. “Cross-linked actin networks (CLANs) in glaucoma”. Experimental Eye Research 159 (2017): 16-22.
  37. De Groef L., et al. “Aberrant collagen composition of the trabecular meshwork results in reduced aqueous humor drainage and elevated IOP in MMP-9 Null Mice”. Investigative Ophthalmology and Visual Science14 (2016): 5984-5995.
  38. Lynch JM., et al. “Binding of a glaucoma-associated myocilin variant to the αB-crystallin chaperone impedes protein clearance in trabecular meshwork cells”. Journal of Biological Chemistry52 (2018): 20137-20156.
  39. Porter K., et al. “Autophagic dysregulation in glaucomatous trabecular meshwork cells”. Biochimica et Biophysica Acta3 (2015): 379-385.
  40. Stamer WD., et al. “Biomechanics of Schlemm's canal endothelium and intraocular pressure reduction”. Progress in Retinal and Eye Research 44 (2015): 86-98.
  41. Alvarado J., et al. “Trabecular meshwork cellularity in primary open-angle glaucoma and nonglaucomatous normal”. Ophthalmology6 (1984): 564-579.
  42. Johnson DH. “Human trabecular meshwork cell survival is dependent on perfusion rate”. Investigative Ophthalmology and Visual Science6 (1996): 1204-1208.
  43. Ying Y., et al. “Activation of ATF4 triggers trabecular meshwork cell dysfunction and apoptosis in POAG”. Aging (Albany NY)6 (2021): 8628-8642.
  44. Zhao Y., et al. “AQP1 suppression by ATF4 triggers trabecular meshwork tissue remodeling in ET-1-induced POAG”. Journal of Cellular and Molecular Medicine6 (2020): 3469-3480.
  45. He Y., et al. “Mitochondrial defects and dysfunction in calcium regulation in glaucomatous trabecular meshwork cells”. Investigative Ophthalmology and Visual Science11 (2008): 4912-4922.
  46. Thomson BR., et al. “Cellular crosstalk regulates the aqueous humor outflow pathway and provides new targets for glaucoma therapies”. Nature Communications1 (2021): 6072.
  47. Thomson BR., et al. “Targeting the vascular-specific phosphatase PTPRB protects against retinal ganglion cell loss in a pre-clinical model of glaucoma”. Elife 8 (2019): e48474.
  48. Wang L-Y., et al. “Progress in the basic and clinical research on the Schlemm’s canal”. International Journal of Ophthalmology 13 (2020): 816-821.
  49. Xu G., et al. “Optic nerve head deformation in glaucoma: the temporal relationship between optic nerve head surface depression and retinal nerve fiber layer thinning”. Ophthalmology 121 (2014): 2362-2370.
  50. Neufeld AH., et al. “Nitric oxide synthase in the human glaucomatous optic nerve head”. Archives of Ophthalmology 115 (1997): 497-503.
  51. Neufeld AH. “Microglia in the optic nerve head and the region of parapapillary chorioretinal atrophy in glaucoma”. Archives of Ophthalmology 117 (1999): 1050-1056.
  52. Burgoyne CF., et al. “The optic nerve head as a biomechanical structure; a new paradigm for understanding the role of IOP-related stress and strain in the pathophysiology of glaucomatous optic nerve head damage”. Progress in Retinal and Eye Research 24 (2005): 39-73.
  53. Daguman IJ and Delfin MS. “Correlation of lamina cribosa and standard automated perimeter findings in glaucoma and non-glaucoma patients”. Journal of Ophthalmology Studies 2 (2018): 1-5.
  54. Downs JC., et al. “Glaucomatous cupping of the lamina cribrosa: a review of the evidence for active progressive remodeling as a mechanism”. Experimental Eye Research 93 (2011): 133-140.
  55. McElnea EM., et al. “Oxidative stress, mitochondrial dysfunction and calcium overload in human lamina cribrosa cells from glaucoma donors”. Molecular Vision 17 (2011): 1182-1189.
  56. McElnea EM., et al. “Lipofuscin accumulation and autophagy in glaucomatous human lamina cribrosa cells”. BMC Ophthalmology 14 (2014): 153.
  57. Adornetto A., et al. “Neuroinflammation as a target for glaucoma therapy”. Neural Regeneration Research 14 (2019): 391-394.
  58. Albalawi F., et al. “The P2X7 Receptor primes IL-1β and the NLRP3 inflammasome in astrocytes exposed to mechanical strain”. Frontiers in Cellular Neuroscience 11 (2017): 227.
  59. Evangelho K., et al. “Pathophysiology of primary open-angle glaucoma from a neuroinflammatory and neurotoxicity perspective: a review of the literature”. International Ophthalmology1 (2019): 259-271.
  60. Parsadaniantz MS., et al. “Glaucoma: a degenerative optic neuropathy related to neuroinflammation?” Cells 9 (2020): 535.
  61. Soto I and Howell GR. “The complex role of neuroinflammation in glaucoma”. Cold Spring Harbor Perspectives in Medicine8 (2014): a017269.
  62. Vernazza S., et al. “Neuroinflammation in primary open-angle glaucoma”. Journal of Clinical Medicine10 (2020): 3172.
  63. Wei X., et al. “Neuroinflammation and microglia in glaucoma: time for a paradigm shift”. Journal of Neuroscience Research1 (2019): 70-76.
  64. Williams PA., et al. “Lasker/IRRF initiative on astrocytes and glaucomatous neurodegeneration participants. Neuroinflammation in glaucoma: a new opportunity”. Experimental Eye Research 157 (2017): 20-27.
  65. Yerramothu P., et al. “Inflammasomes, the eye and anti-inflammasome therapy”. Eye3 (2018): 491-505.
  66. Russo R., et al. “Retinal ganglion cell death in glaucoma: exploring the role of neuroinflammation”. European Journal of Pharmacology 787 (2016): 134-142.
  67. Rashid K., et al. “Microglia in retinal degeneration”. Frontiers in Immunology 10 (2019): 1975.
  68. Quillen S., et al. “Astrocyte responses to experimental glaucoma in mouse optic nerve head”. PLoS One8 (2020): e0238104.
  69. Tribble JR., et al. “Ocular hypertension suppresses homeostatic gene expression in optic nerve head microglia of DBA/2 J mice”. Molecular Brain1 (2020) : 81.
  70. Yi SY., et al. “Microglial Density Alters Measures of Axonal Integrity and Structural Connectivity”. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging11 (2020): 1061-1068.
  71. Bosco A., et al. “Early microglia activation in a mouse model of chronic glaucoma”. The Journal of Comparative Neurology 519 (2011): 599-620.
  72. Ebneter A., et al. “Microglial activation in the visual pathway in experimental glaucoma: spatiotemporal characterization and correlation with axonal injury”. Investigative Ophthalmology and Visual Science 51 (2010): 6448-6460.
  73. Hernandez MR., et al. “Age-related changes in the extracellular matrix of the human optic nerve head”. American Journal of Ophthalmology 107 (1989): 476-484.
  74. Chintala SK. “The emerging role of proteases in retinal ganglion cell death”. Experimental Eye Research1 (2006): 5-12.
  75. Chintala SK., et al. “Activation of TLR3 promotes the degeneration of retinal ganglion cells by upregulating the protein levels of JNK3”. Investigative Ophthalmology and Visual Science 56 (2015): 505-514.
  76. Roh M., et al. “Etanercept, a widely used inhibitor of tumor necrosis factor-alpha (TNF-alpha), prevents retinal ganglion cell loss in a rat model of glaucoma”. PLoS ONE 7 (2012): e40065.
  77. Dvoriantchikova G and Ivanov D. “Tumor necrosis factor-alpha mediates activation of NF-κB and JNK signaling cascades in retinal ganglion cells and astrocytes in opposite ways”. European Journal of Neuroscience 40 (2014): 3171-3178.
  78. Hu H., et al. “Stimulation of the P2X7 receptor kills rat retinal ganglion cells in vivo”. Experimental Eye Research 91 (2010): 425-432.
  79. Poyomtip T. “Roles of Toll-Like receptor 4 for cellular pathogenesis in primary open-angle glaucoma: a potential therapeutic strategy”. Journal of Microbiology, Immunology and Infection2 (2019): 201-206.
  80. Wilson GN., et al. “Early pro-inflammatory cytokine elevations in the DBA/2J mouse model of glaucoma”. Journal of Neuroinflammation 12 (2015): 176.
  81. Stokely ME., et al. “Effects of endothelin-1 on components of anterograde axonal transport in optic nerve”. Investigative Ophthalmology and Visual Science10 (2002): 3223-3230.
  82. Prassana G., et al. “Endothelin, astrocytes and glaucoma”. Experimental Eye Research 93 (2011): 170-177.
  83. Chaphalkar RM., et al. “Endothelin-1 mediated decrease in mitochondrial gene expression and bioenergetics contribute to neurodegeneration of retinal ganglion cells”. Scientific Reports1 (2020): 3571.
  84. Resta V., et al. “Acute retinal ganglion cell injury caused by intraocular pressure spikes is mediated by endogenous extracellular ATP”. European Journal of Neuroscience 25 (2007): 2741-2754.
  85. Schneemann A., et al. “Elevation of nitric oxide production in human trabecular meshwork by increased pressure”. Graefe's Archive for Clinical and Experimental Ophthalmology4 (2003): 321-326.
  86. Fu CT and Sretavan DW. “Ectopic vesicular glutamate release at the optic nerve head and axon loss in mouse experimental glaucoma”. The Journal of Neuroscience45 (2012): 15859-15876.
  87. Januschowski K., et al. “Glutamate and hypoxia as a stress model for the isolated perfused vertebrate retina”. The Journal of Visualized Experiments 22 (2015): 97.
  88. Howell GR., et al. “Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma”. Journal of Cell Biology7 (2007): 1523-1537.
  89. Howell GR., et al. “Molecular clustering identifies complement and endothelin induction as early events in a mouse model of glaucoma”. Journal of Clinical Investigation 121 (2011): 1429- 1444.
  90. Hollander H., et al. “Evidence of constriction of optic axons at the lamina cribrosa in the normotensive eye in humans and other mammals”. Ophthalmic Research 127 (1995): 296-309.
  91. Anderson DR and Hendrickson A. “Effect of intraocular pressure on rapid axoplasmic transport in monkey optic nerve”. Investigative Ophthalmology10 (1974): 771-783.
  92. Pease ME., et al. “Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma”. Investigative Ophthalmology and Visual Science 41 (2000): 764-774.
  93. Crish SD., et al. “Distal axonopathy with structural persistence in glaucomatous neurodegeneration”. Proceedings of the National Academy of Sciences of the United States of America (U S A). 107 (2010): 5196-5201.
  94. Crish SD., et al. “Failure of axonal transport induces a spatially coincident increase in astrocyte BDNF prior to synapse loss in a central target”. The Journal of Neuroscience 229 (2013): 55-70.
  95. Dengler-Crish CM., et al. “Anterograde transport blockade precedes deficits in retrograde transport in the visual projection of the DBA/2J mouse model of glaucoma”. Frontiers in Neuroscience 8 (2014): 290.
  96. Cooper ML., et al. “Early astrocyte redistribution in the optic nerve precedes axonopathy in the DBA/2J mouse model of glaucoma”. Experimental Eye Research 150 (2016): 22-33.
  97. Dai Y., et al. “Astrocytic responses in the lateral geniculate nucleus of monkeys with experimental glaucoma”. Veterinary Ophthalmology1 (2012): 23-30.
  98. Lam D., et al. “Astrocyte and microglial activation in the lateral geniculate nucleus and visual cortex of glaucomatous and optic nerve transected primates”. Molecular Vision 15 (2009): 2217-2229.
  99. Calkins DJ and Horner PJ. “The cell and molecular biology of glaucoma: axonopathy and the brain”. Investigative Ophthalmology and Visual Science 53 (2012): 2482-2484.
  100. Silverman SM., et al. “C1q propagates microglial activation and neurodegeneration in the visual axis following retinal ischemia/reperfusion injury”. Molecular Neurodegeneration 11 (2016): 24.
  101. Nickells RW., et al. “Under pressure: Cellular and molecular responses during glaucoma, a common neurodegeneration with axonopathy”. Annual Review of Neuroscience 35 (2012): 153-179.
  102. Stasi K., et al. “Complement component 1Q (C1Q) upregulation in retina of murine, primate, and human glaucomatous eyes”. Investigative Ophthalmology and Visual Science 3 (2006): 1024-1029.
  103. Harder JM., et al. “Complement peptide C3a receptor 1 promotes optic nerve degeneration in DBA/2J mice”. Journal of Neuroinflammation 1 (2020): 336.
  104. Duce JA., et al. “Activation of arly components of complement targets myelin and oligodendrocytes in the aged rhesus monkey brain”. Neurobiology of Aging 4 (2006): 633-644.
  105. Levin LA., et al. “Lasker/IRRF Initiative on Astrocytes and Glaucomatous Neurodegeneration Participants. Neuroprotection for glaucoma: Requirements for clinical translation”. Experimental Eye Research 157 (2017): 34-37.
  106. Williams PA., et al. “Retinal ganglion cell dendritic atrophy in DBA/2J glaucoma”. PLoS One8 (2013): e72282.
  107. Williams PA., et al. “Inhibition of the classical pathway of the complement cascade prevents early dendritic and synaptic degeneration in glaucoma”. Molecular Neurodegeneration 11 (2016): 26.
  108. Sapienza A., et al. “Bilateral neuroinflammatory processes in visual pathways induced by unilateral ocular hypertension in the rat”. Journal of Neuroinflammation 13 (2016): 44.
  109. Sasaoka M., et al. “Changes in visual fields and lateral geniculate nucleus in monkey laser-induced high intraocular pressure model”. Experimental Eye Research 86 (2008): 770-782.
  110. Gupta N., et al. “Chronic ocular hypertension induces dendrite pathology in the lateral geniculate nucleus of the brain”. Experimental Eye Research 84 (2007): 176-184.
  111. Yucel YH., et al. “Atrophy of relay neurons in magno- and parvocellular layers in the lateral geniculate nucleus in experimental glaucoma”. Investigative Ophthalmology and Visual Science 42 (2001): 3216-3222.
  112. Yu L., et al. “Progressive thinning of visual cortex in primary open-angle glaucoma of varying severity”. PLoS One 10 (2015): e0121960.
  113. Maddineni P., et al. “CNS axonal degeneration and transport deficits at the optic nerve head precede structural and functional loss of retinal ganglion cells in a mouse model of glaucoma”. Molecular Neurodegeneration 1 (2020): 48.
  114. Flemming A. “Bacteria-primed T cells identified as culprit in glaucoma”. Nature Reviews Immunology 10 (2018): 603.
  115. Crabb DP. “A view on glaucoma-are we seeing it clearly?” Eye 30 (2016): 304-313.
  116. Caprioli J and Coleman AL. “Intraocular pressure fluctuation a risk factor for visual field progression at low intraocular pressures in the advanced glaucoma intervention study”. Ophthalmology 115 (2008): 1123-1129.
  117. Bengtsson B., et al. “Fluctuation of intraocular pressure and glaucoma progression in the early manifest glaucoma trial”. Ophthalmology 114 (2007): 205-209.
  118. Kim JH and Caprioli J. “Intraocular pressure fluctuation: is it important?” Journal of Ophthalmic and Vision Research 3 (2018): 170-174.
  119. Geyer O and Levo Y. “Glaucoma is an autoimmune disease”. Autoimmunity Reviews 6 (2020): 102535.
  120. Tezel G., et al. “Oxidative stress and the regulation of complement activation in human glaucoma”. Investigative Ophthalmology and Visual Science 51 (2010): 5071-5082.
  121. Patel G., et al. “Molecular taxonomy of human ocular outflow tissues defined by single-cell transcriptomics”. Proceedings of the National Academy of Sciences of the United States of America 13 (2020): 12856-12867.
  122. Babizhayev MA and Yegorov YE. “Senescent phenotype of trabecular meshwork cells displays biomarkers in primary open-angle glaucoma”. Current Molecular Medicine 7 (2011): 528-552.
  123. Buffault J., et al. “The trabecular meshwork: Structure, function and clinical implications. A review of the literature”. Journal Francais d'Ophtalmologie 7 (2020): e217-e230.
  124. Baden T., et al. “The functional diversity of retinal ganglion cells in the mouse”. Nature 529 (2016): 345-350.
  125. Della Santina L and Ou Y. “Who's lost first? Susceptibility of retinal ganglion cell types in experimental glaucoma”. Experimental Eye Research 158 (2017): 43-50.
  126. Ou Y., et al. “Selective vulnerability of specific retinal ganglion cell types and synapses after transient ocular hypertension”. The Journal of Neuroscience 35 (2016): 9240-9252.
  127. Quigley HA., et al. “Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma”. American Journal of Ophthalmology 107 (1989): 453-464.
  128. Osborne NN., et al. “Glaucoma: focus on mitochondria in relation to pathogenesis and neuroprotection”. European Journal of Pharmacology 787 (2016): 127-133.
  129. Park H-Y L., et al. “Torsion of the optic nerve head is a prominent feature of normal-tension glaucoma”. Investigative Ophthalmology and Visual Science (2015): 156-163.
  130. Nuschke AC., et al. “Assessment of retinal ganglion cell damage in glaucomatous optic neuropathy: axon transport, injury and soma loss”. Experimental Eye Research 141 (2015): 111-124.
  131. Trivedi V., et al. “Widespread brain reorganization perturbs visuomotor coordination in early glaucoma”. Scientific Reports 1 (2019): 14168.
  132. Bhandari A., et al. “Early-stage ocular hypertension alters retinal ganglion cell synaptic transmission in the visual thalamus”. Frontiers in Cellular Neuroscience 13 (2019): 426.
  133. Bham HA., et al. “Unaltered perception of suprathreshold contrast in early glaucoma despite sensitivity loss”. Investigative Ophthalmology and Visual Science 61 (2020): 23.
  134. AGIS Investigators. “The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration”. American Journal of Ophthalmology 130 (2000): 429-440.
  135. Heijl A., et al. “Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial”. Archives of Ophthalmology 120 (2002): 1268-1279.
  136. Kass MA., et al. “The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma”. Archives of Ophthalmology 6 (2002): 701-713.
  137. CNTGSG- Collaborative Normal-Tension Glaucoma Study Group. “The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma”. American Journal of Ophthalmology 126 (1998a): 498-505.
  138. Hellberg MR., et al. “Identification and characterization of the ocular hypotensive efficacy of Travoprost, a potent and selective FP prostaglandin receptor agonist, and AL-6598, a DP prostaglandin receptor agonist”. Survey of Ophthalmology 47 (2002): S13-S33.
  139. Chauhan BC and Drance SM. “The relationship between intraocular pressure and visual field progression in glaucoma”. Graefe's Archive for Clinical and Experimental Ophthalmology 230 (1992): 521-526.
  140. Musch DC., et al. “Intraocular pressure control and long-term visual field loss in the Collaborative Initial Glaucoma Treatment Study”. Ophthalmology 9 (2011): 1766-1773.
  141. Lee EJ., et al. “Reversal of lamina cribrosa displacement after intraocular pressure reduction in open-angle glaucoma”. Ophthalmology 120 (2013): 553-559.
  142. Sehi M., et al. “Reversal of retinal ganglion cell dysfunction after surgical reduction of intraocular pressure”. Ophthalmology 117 (2010): 2329-2336.
  143. Tu S., et al. “Relationship between intraocular pressure and retinal nerve fibre thickness loss in a monkey model of chronic ocular hypertension”. Eye12 (2019): 1833-1841.
  144. Torres LA and Hatanaka M. “Correlating structural and functional damage in glaucoma”. Journal of Glaucoma 12 (2019) : 1079-1085.
  145. Bhandari A., et al. “Effect of surgery on visual field progression in normal-tension glaucoma”. Ophthalmology 104 (1997): 1131-1137.
  146. Stjernschantz J and Alm A. “Latanoprost as a new horizon in the medical management of glaucoma”. Current Opinion in Ophthalmology 2 (1996): 11-17.
  147. Toris CB., et al. “Update on the mechanism of action of topical prostaglandins for intraocular pressure reduction”. Survey of Ophthalmology 1 (2008): S107-120.
  148. Kirihara T., et al. “Pharmacologic characterization of omidenepag isopropyl, a novel selective EP2 receptor agonist, as an ocular hypotensive agent”. Investigative Ophthalmology and Visual Science 59 (2018): 145-153.
  149. Fuwa M., et al. “Effects of a novel selective EP2 receptor agonist, omidenepag isopropyl, on aqueous humor dynamics in laser-induced ocular hypertensive monkeys”. Journal of Ocular Pharmacology and Therapeutics 7 (2018): 531-537.
  150. Fuwa M., et al. “Additive intraocular pressure-lowering effects of a novel selective EP2 receptor agonist, omidenepag isopropyl, combined with existing antiglaucoma agents in conscious ocular normotensive monkeys”. Journal of Ocular Pharmacology and Therapeutics 4 (2021): 223-229.
  151. Duggan S. “Omidenepag isopropyl ophthalmic solution 0.002%: first global approval”. Drugs 78 (2018): 1925-1929.
  152. Ferro Desideri L., et al. “Omidenepag isopropyl for the treatment of glaucoma and ocular hypertension”. Drugs Today 55 (2019): 377-384.
  153. Aihara M., et al. “Omidenepag Isopropyl versus latanoprost in primary open-angle glaucoma and ocular hypertension: The Phase 3 AYAME Study”. American Journal of Ophthalmology 220 (2020a): 53-63.
  154. Aihara M., et al. “Intraocular pressure-lowering effect of omidenepag isopropyl in latanoprost non-/low-responder patients with primary open-angle glaucoma or ocular hypertension: the FUJI study”. The Japanese Journal of Ophthalmology 4 (2020b): 398-406.
  155. Sharif NA., et al. “A novel non-prostaglandin EP2-receptor agonist for glaucoma treatment: Omidenepag Isopropyl (DE-117)”. The FASEB Journal 34 (2020): 8817.
  156. Sharif NA., et al. “Human ciliary muscle responses to FP-class prostaglandin analogs: phosphoinositide hydrolysis, intracellular Ca2+ mobilization and MAP kinase activation”. Journal of Ocular Pharmacology and Therapeutics 19 (2003): 437-455.
  157. Sharif NA., et al. “Human trabecular meshwork cell responses induced by bimatoprost, travoprost, unoprostone, and other FP prostaglandin receptor agonist analogues”. Investigative Ophthalmology and Visual Science 44 (2003): 715-721.
  158. Cavet ME and DeCory HH. “The Role of Nitric Oxide in the Intraocular Pressure Lowering Efficacy of Latanoprostene Bunod: Review of Nonclinical Studies”. Journal of Ocular Pharmacology and Therapeutics 1-2 (2018): 52-60.
  159. Dismuke WM., et al. “Human trabecular meshwork cell volume decrease by NO-independent soluble guanylate cyclase activators YC-1 and BAY-58-2667 involves the BKCa ion channel”. Investigative Ophthalmology and Visual Science 50 (2009): 3353-3359.
  160. Dismuke WM., et al. “Endogenous regulation of human Schlemm’s canal cell volume by nitric oxide signaling”. Investigative Ophthalmology and Visual Science 51 (2010): 5817-5824.
  161. Dikopf MS., et al. “Topical treatment of glaucoma: established and emerging pharmacology”. Expert Opinion on Pharmacotherapy 9 (2017): 885-898.
  162. Lin CW., et al. “Discovery and preclinical development of netarsudil, a novel ocular hypotensive agent for the treatment of glaucoma”. Journal of Ocular Pharmacology and Therapeutics 1-2 (2018): 40-51.
  163. Li G., et al. “A small molecule inhibitor of VE-PTP activates Tie2 in Schlemm's canal increasing outflow facility and reducing intraocular pressure”. Investigative Ophthalmology and Visual Science 14 (2020): 12.
  164. Roy Chowdhury U., et al. “ATP sensitive potassium channel openers: A new class of ocular hypotensive agents”. Experimental Eye Research 158 (2017): 85-93.
  165. Savinainen A., et al. “Pharmacokinetics and intraocular pressure-lowering activity of TAK-639, a novel C-type natriuretic peptide analog, in rabbit, dog, and monkey”. Experimental Eye Research 189 (2019): 107836.
  166. Asrani S., et al. “Fixed-dose combination of netarsudil and latanoprost in ocular hypertension and open-angle glaucoma: pooled efficacy/safety analysis of phase 3 MERCURY-1 and -2”. Advances in Therapy 4 (2020): 1620-1631.
  167. Hollo G., et al. “Fixed-combination intraocular pressure-lowering therapy for glaucoma and ocular hypertension: advantages in clinical practice”. Expert Opinion on Pharmacotherapy 15 (2014): 1737-1747.
  168. Geffen N., et al. “Laser-assisted techniques for penetrating and nonpenetrating glaucoma surgery”. Developments in Ophthalmology 59 (2017): 100-112.
  169. Garg A and Gazzard G. “Selective laser trabeculoplasty: past, present, and future”. Eye (Lond). 32.5 (2018): 863-876.
  170. Pillunat LE., et al. “Micro-invasive glaucoma surgery (MIGS): a review of surgical procedures using stents”. Clinical Ophthalmology 11 (2017): 1583-1600.
  171. Ansari E. “An update on implants for minimally invasive glaucoma surgery (MIGS)”. Ophthalmology and Therapy 2 (2017): 233-241.
  172. Pahlitzsch M., et al. “Is there a change in the quality of life comparing the micro-invasive glaucoma surgery (MIGS) and the filtration technique trabeculectomy in glaucoma patients?” Graefe's Archive for Clinical and Experimental Ophthalmology 2 (2017): 351-357.
  173. Nichani P., et al. “Micro-invasive glaucoma surgery: A Review of 3476 Eyes”. Survey of Ophthalmology S0039-S6257 (2020): 30135-30131.
  174. Sadruddin O., et al. “Ab externo implantation of the MicroShunt, a poly (styrene-block-isobutylene-blockstyrene) surgical device for the treatment of primary open-angle glaucoma: a review”. Eye Vision 6 (2019): 36.
  175. He S., et al. “Targets of neuroprotection in glaucoma”. Journal of Ocular Pharmacology and Therapeutics 1-2 (2018): 85-106.
  176. Khatib TZ and Martin KR. “Protecting retinal ganglion cells”. Eye2 (2017): 218-224.
  177. Khatib TZ., et al. “Receptor-ligand supplementation via a self-cleaving 2A peptide-based gene therapy promotes CNS axonal transport with functional recovery”. Science Advances 14 (2021): eabd2590.
  178. Saccà SC., et al. “Substances of interest that support glaucoma therapy”. Nutrients2 (2019): 239.
  179. Scuteri D., et al. “Impact of nutraceuticals on glaucoma: A systematic review”. Progress in Brain Research 257 (2020): 141-154.
  180. Cammalleri M., et al. “A dietary combination of forskolin with homotaurine, spearmint and b vitamins protects injured retinal ganglion cells in a rodent model of hypertensive glaucoma”. Nutrients4 (2020): 1189.
  181. Aksar AT., et al. “Neuroprotective effect of edaravone in experimental glaucoma model in rats: a immunofluorescence and biochemical analysis”. International Journal of Ophthalmology 2 (2015): 239-244.
  182. Ammar DA., et al. “Antioxidants protect trabecular meshwork cells from hydrogen peroxide-induced cell death”. Translational Vision Science and Technology 1 (2012): 4.
  183. Almasieh M and Levin LA. “Neuroprotection in glaucoma: animal models and clinical trials”. The Annual Review of Vision Science 3 (2017): 91-120.
  184. Goldberg JL. “Role of electrical activity in promoting neural repair”. Neuroscience Letters 519 (2012): 134-137.
  185. Pardue MT and Allen RS. “Neuroprotective strategies for retinal disease”. Progress in Retinal and Eye Research 65 (2018): 50-76.
  186. Sharif NA. “Glaucomatous optic neuropathy treatment options: the promise of novel therapeutics, techniques and tools to help preserve vision”. Neural Regeneration Research 13 (2018b): 1145-1150.
  187. Howell GR., et al. “Combinatorial targeting of early pathways profoundly inhibits neurodegeneration in a mouse model of glaucoma”. Neurobiology of Disease 71 (2014): 44-52.
  188. Marc R., et al. “Retinal prosthetics, optogenetics, and chemical photoswitches”. ACS Chemical Neuroscience 10 (2014): 895-901.
  189. Tochitsky I and Kramer RH. “Optopharmacological tools for restoring visual function in degenerative retinal diseases”. Current Opinion in Neurobiology 34 (2015): 74-78.
  190. Nin-Hill A., et al. “Photopharmacology of ion channels through the light of the computational microscope”. International Journal of Molecular Sciences 21 (2021): 12072.
  191. Mohanty SK and Lakshminarayananan V. “Optical techniques in optogenetics”. Journal of Modern Optics 12 (2015): 949-970.
  192. Sahel JA., et al. “Partial recovery of visual function in a blind patient after optogenetic therapy”. Nature Medicine 7 (2021): 1223-1229.
  193. Hui F., et al. “Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: A crossover randomized clinical trial”. Clinical and Experimental Ophthalmology (2020).
  194. Williams PA., et al. “Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice”. Science6326 (2017): 756-760.
  195. Chou TH., et al. “Nicotinamide-rich diet in DBA/2J mice preserves retinal ganglion cell metabolic function as assessed by PERG adaptation to flicker”. Nutrients7 (2020): 1910.
  196. Clarke SC., et al. “Multispecific antibody development platform based on human heavy chain antibodies”. Frontiers in Immunology 9 (2019): 3037.
  197. Zhong X and D'Antona AM. “Recent advances in the molecular design and applications of multispecific biotherapeutics”. Antibodies (Basel).2 (2021): 13.
  198. Chamling X., et al. “The potential of human stem cells for the study and treatment of glaucoma”. Investigative Ophthalmology and Visual Science 57 (2016): ORSFi1-ORSFi6.
  199. Harrell CR., et al. “Therapeutic potential of mesenchymal stem cells and their secretome in the treatment of glaucoma”. Stem Cells International (2019): 7869130.
  200. Zhu W., et al. “Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo”. Proceedings of the National Academy of Sciences of the United States of America (USA) 113 (2016): E3492-E3500.
  201. Zhu W., et al. “Restoration of aqueous humor outflow following transplantation of iPSC derived trabecular meshwork cells in a transgenic mouse model of glaucoma”. Investigative Ophthalmology and Visual Science 58 (2017): 2054-2062.
  202. Dismuke WM., et al. “Mechanism of fibronectin binding to human trabecular meshwork exosomes and its modulation by dexamethasone”. PLoS One 11.10 (2016): e0165326.
  203. Li YC., et al. “Mesenchymal stem cell-derived exosomes protect trabecular meshwork from oxidative stress”. Scientific Reports 1 (2021): 14863.
  204. Takahashi E., et al. “The effects of exosomes derived from trabecular meshwork cells on Schlemm's canal endothelial cells”. Scientific Reports 1 (2021): 21942.
  205. Mead B and Tomarev S. “Retinal ganglion cell neuroprotection by growth factors and exosomes: lessons from mesenchymal stem cells”. Neural Regeneration Research 2 (2018): 228-229.
  206. Aires ID., et al. “Exosomes derived from microglia exposed to elevated pressure amplify the neuroinflammatory response in retinal cells”. Glia12 (2020): 2705-2724.
  207. Cui Y., et al. “Protective effects of intravitreal administration of mesenchymal stem cell-derived exosomes in an experimental model of optic nerve injury”. Experimental Cell Research 1 (2021): 112792.
  208. Luna C., et al. “Regulation of trabecular meshwork cell contraction and intraocular pressure by MiR-200c”. PloS One 7 (2012): 251688.
  209. Luna C., et al. “Long-term decrease of intraocular pressure in rats by viral delivery of miR-146a”. Translational Vision Science and Technology 8 (2021): 14.
  210. Li S., et al. “Intravitreal transplants of Schwann cells and fibroblasts promote the survival of axotomized retinal ganglion cells in rats”. Brain Research 1029 (2004): 56-64.
  211. Smedowski A., et al. “Predegenerated Schwann cells--a novel prospect for cell therapy for glaucoma: neuroprotection, neuroregeneration and neuroplasticity”. Scientific Reports 6 (2016): 23187.
  212. Fang Y., et al. “A new type of Schwann cell graft transplantation to promote optic nerve regeneration in adult rats”. Journal of Tissue Engineering and Regenerative Medicine 4 (2010): 581-589.
  213. Hu Y., et al. “Lentiviral-mediated transfer of CNTF to Schwann cells within reconstructed peripheral nerve grafts enhances adult retinal ganglion cell survival and axonal regeneration”. Gene Therapy 11 (2005): 906-915.
  214. Johnson TV and Martin KR. “Cell transplantation approaches to retinal ganglion cell neuroprotection in glaucoma”. Current Opinion in Pharmacology 13 (2013): 78‑
  215. Chen M., et al. “Mitochondria-targeted peptide MTP-131 alleviates mitochondrial dysfunction and oxidative damage in human trabecular meshwork cells”. Investigative Ophthalmology and Visual Science 10 (2011): 7027-7037.
  216. Ellis DZ., et al. “Sigma-1 receptor regulates mitochondrial function in glucose- and oxygen-deprived retinal ganglion cells”. Investigative Ophthalmology and Visual Science 5 (2017): 2755-2764.
  217. Davis BM., et al. “Topical Coenzyme Q10 demonstrates mitochondrial-mediated neuroprotection in a rodent model of ocular hypertension”. Mitochond (2017): 30142-30143.
  218. He JN., et al. “Rapamycin removes damaged mitochondria and protects human trabecular meshwork (TM-1) cells from chronic oxidative stress”. Molecular Neurobiology 9 (2019): 6586-6593.
  219. Ju WK., et al. “Increased mitochondrial fission and volume density by blocking glutamate excitotoxicity protect glaucomatous optic nerve head astrocytes”. Glia5 (2015): 736-753.
  220. Lee D., et al. “Coenzyme Q10 ameliorates oxidative stress and prevents mitochondrial alteration in ischemic retinal injury”. Apoptosis4 (2014): 603-614.
  221. Rao VR and Stubbs EB Jr. “TGF-β2 promotes oxidative stress in human trabecular meshwork cells by selectively enhancing NADPH oxidase 4 expression”. Investigative Ophthalmology and Visual Science 4 (2021): 4.
  222. Wentz-Hunter K., et al. “Myocilin is associated with mitochondria in human trabecular meshwork cells”. Journal of Cellular Physiology 1 (2002): 46-53.
  223. Zhou B., et al. “Facilitation of axon regeneration by enhancing mitochondrial transport and rescuing energy deficits”. Journal of Cell Biology 1 (2016): 103-119.
  224. Yang L., et al. “Rescue of glaucomatous neurodegeneration by differentially modulating neuronal endoplasmic reticulum stress molecules”. The Journal of Neuroscience21 (2016): 5891-5903.
  225. Bosco A., et al. “Complement C3-targeted gene therapy restricts onset and progression of neurodegeneration in chronic mouse glaucoma”. Molecular Therapy 26 (2018): 2379-2396.
  226. Boia R., et al. “Neuroprotective strategies for retinal ganglion cell degeneration: current status and challenges ahead”. International Journal of Molecular Sciences 7 (2020): 2262.
  227. Fernandes KA., et al. “DLK-dependent signaling is important for somal but not axonal degeneration of retinal ganglion cells following axonal injury”. Neurobiology of Disease 69 (2014): 108-116.
  228. Guymer C., et al. “Neuroprotection in glaucoma: recent advances and clinical translation”. Clinical and Experimental Ophthalmology 47 (2019): 88-105.
  229. Jain A., et al. “CRISPR-Cas9-based treatment of myocilin associated glaucoma”. Proceedings of the National Academy of Sciences of the United States of America 114 (2017): 11199-11204.
  230. Ittoop SM., et al. “Current opinion in ophthalmology: novel glaucoma devices in the pipeline”. Current Opinion in Ophthalmology 2 (2019): 117-124.
  231. Kasi A., et al. “In vivo imaging of structural, metabolic and functional brain changes in glaucoma”. Neural Regeneration Research 3 (2019): 446-449.
  232. Li HJ., et al. “Exploring optic nerve axon regeneration”. Current Neuropharmacology 6 (2017): 861-873.
  233. Liu R., et al. “Effect of alpha lipoic acid on retinal ganglion cell survival in an optic nerve crush model”. Molecular Vision 22 (2016): 1122-1136.
  234. Lusthaus J and Goldberg I. “Current management of glaucoma”. Medical Journal of Australia 4 (2019): 180-187.
  235. Mak HK., et al. “Impact of PTEN/SOCS3 deletion on amelioration of dendritic shrinkage of retinal ganglion cells after optic nerve injury”. Experimental Eye Research 192 (2020): 107938.
  236. Pang Y., et al. “Mitochondria-targeted antioxidant SS-31 is a potential novel ophthalmic medication for neuroprotection in glaucoma”. Medical Hypothesis, Discovery and Innovation in Ophthalmology 3 (2015): 120-126.
  237. Patel AK., et al. “Wnt signaling promotes axonal regeneration following optic nerve injury in the mouse”. Neurosci 343 (2017): 372-383.
  238. Soto I., et al. “Retinal ganglion cell loss in a rat ocular hypertension model is sectorial and involves early optic nerve axon loss”. Investigative Ophthalmology and Visual Science 52 (2011): 434-441.
  239. Thomson BR., et al. “A lymphatic defect causes ocular hypertension and glaucoma in mice”. Journal of Clinical Investigation 10 (2014): 4320-4324.
  240. Tsai JC. “Innovative IOP-independent neuroprotection and neuroregeneration strategies in the pipeline for glaucoma”. Journal of Ophthalmology (2020): 9329310.
  241. Wang X., et al. “Intravitreal delivery of human NgR-Fc decoy protein regenerates axons after optic nerve crush and protects ganglion cells in glaucoma models”. Investigative Ophthalmology and Visual Science 2 (2015): 1357-1366.
  242. Weinreb RN., et al. “Oral Memantine for the treatment of glaucoma: design and results of 2 randomized, placebo-controlled, phase 3 studies”. Ophthalmology 125 (2018): 1874-1885.
  243. Yang X., et al. “Neurodegenerative and inflammatory pathway components linked to TNF-alpha/TNFR1 signaling in the glaucomatous human retina”. Investigative Ophthalmology and Visual Science 52 (2011): 8442-8454.
  244. Yang X., et al. “Transgenic inhibition of astroglial NF-κB restrains the neuroinflammatory and neurodegenerative outcomes of experimental mouse glaucoma”. Journal of Neuroinflammation 1 (2020): 252.
  245. Zheng C., et al. “Artificial intelligence in glaucoma”. Current Opinion in Ophthalmology 2 (2019): 97-103.
  246. Wu J., et al. “Gene therapy for glaucoma by ciliary body aquaporin 1 disruption using CRISPR-Cas9”. Molecular Therapy 3 (2020): 820-829.
Citation: Najam A Sharif. “Pathogenesis of Elevated Intraocular Pressure and Glaucoma-Related Retinal and Optic Nerve Degeneration: Diverse Mitigation Strategies and Treatment Modalities”. EC Ophthalmology 13.6 (2022): 43-67.

PubMed Indexed Article

EC Pharmacology and Toxicology
LC-UV-MS and MS/MS Characterize Glutathione Reactivity with Different Isomers (2,2' and 2,4' vs. 4,4') of Methylene Diphenyl-Diisocyanate.

PMID: 31143884 [PubMed]

PMCID: PMC6536005

EC Pharmacology and Toxicology
Alzheimer's Pathogenesis, Metal-Mediated Redox Stress, and Potential Nanotheranostics.

PMID: 31565701 [PubMed]

PMCID: PMC6764777

EC Neurology
Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

PMID: 27747317 [PubMed]

PMCID: PMC5065347

EC Pharmacology and Toxicology
Will Blockchain Technology Transform Healthcare and Biomedical Sciences?

PMID: 31460519 [PubMed]

PMCID: PMC6711478

EC Pharmacology and Toxicology
Is it a Prime Time for AI-powered Virtual Drug Screening?

PMID: 30215059 [PubMed]

PMCID: PMC6133253

EC Psychology and Psychiatry
Analysis of Evidence for the Combination of Pro-dopamine Regulator (KB220PAM) and Naltrexone to Prevent Opioid Use Disorder Relapse.

PMID: 30417173 [PubMed]

PMCID: PMC6226033

EC Anaesthesia
Arrest Under Anesthesia - What was the Culprit? A Case Report.

PMID: 30264037 [PubMed]

PMCID: PMC6155992

EC Orthopaedics
Distraction Implantation. A New Technique in Total Joint Arthroplasty and Direct Skeletal Attachment.

PMID: 30198026 [PubMed]

PMCID: PMC6124505

EC Pulmonology and Respiratory Medicine
Prevalence and factors associated with self-reported chronic obstructive pulmonary disease among adults aged 40-79: the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PMID: 30294723 [PubMed]

PMCID: PMC6169793

EC Dental Science
Important Dental Fiber-Reinforced Composite Molding Compound Breakthroughs

PMID: 29285526 [PubMed]

PMCID: PMC5743211

EC Microbiology
Prevalence of Intestinal Parasites Among HIV Infected and HIV Uninfected Patients Treated at the 1o De Maio Health Centre in Maputo, Mozambique

PMID: 29911204 [PubMed]

PMCID: PMC5999047

EC Microbiology
Macrophages and the Viral Dissemination Super Highway

PMID: 26949751 [PubMed]

PMCID: PMC4774560

EC Microbiology
The Microbiome, Antibiotics, and Health of the Pediatric Population.

PMID: 27390782 [PubMed]

PMCID: PMC4933318

EC Microbiology
Reactive Oxygen Species in HIV Infection

PMID: 28580453 [PubMed]

PMCID: PMC5450819

EC Microbiology
A Review of the CD4 T Cell Contribution to Lung Infection, Inflammation and Repair with a Focus on Wheeze and Asthma in the Pediatric Population

PMID: 26280024 [PubMed]

PMCID: PMC4533840

EC Neurology
Identifying Key Symptoms Differentiating Myalgic Encephalomyelitis and Chronic Fatigue Syndrome from Multiple Sclerosis

PMID: 28066845 [PubMed]

PMCID: PMC5214344

EC Pharmacology and Toxicology
Paradigm Shift is the Normal State of Pharmacology

PMID: 28936490 [PubMed]

PMCID: PMC5604476

EC Neurology
Examining those Meeting IOM Criteria Versus IOM Plus Fibromyalgia

PMID: 28713879 [PubMed]

PMCID: PMC5510658

EC Neurology
Unilateral Frontosphenoid Craniosynostosis: Case Report and a Review of the Literature

PMID: 28133641 [PubMed]

PMCID: PMC5267489

EC Ophthalmology
OCT-Angiography for Non-Invasive Monitoring of Neuronal and Vascular Structure in Mouse Retina: Implication for Characterization of Retinal Neurovascular Coupling

PMID: 29333536 [PubMed]

PMCID: PMC5766278

EC Neurology
Longer Duration of Downslope Treadmill Walking Induces Depression of H-Reflexes Measured during Standing and Walking.

PMID: 31032493 [PubMed]

PMCID: PMC6483108

EC Microbiology
Onchocerciasis in Mozambique: An Unknown Condition for Health Professionals.

PMID: 30957099 [PubMed]

PMCID: PMC6448571

EC Nutrition
Food Insecurity among Households with and without Podoconiosis in East and West Gojjam, Ethiopia.

PMID: 30101228 [PubMed]

PMCID: PMC6086333

EC Ophthalmology
REVIEW. +2 to +3 D. Reading Glasses to Prevent Myopia.

PMID: 31080964 [PubMed]

PMCID: PMC6508883

EC Gynaecology
Biomechanical Mapping of the Female Pelvic Floor: Uterine Prolapse Versus Normal Conditions.

PMID: 31093608 [PubMed]

PMCID: PMC6513001

EC Dental Science
Fiber-Reinforced Composites: A Breakthrough in Practical Clinical Applications with Advanced Wear Resistance for Dental Materials.

PMID: 31552397 [PubMed]

PMCID: PMC6758937

EC Microbiology
Neurocysticercosis in Child Bearing Women: An Overlooked Condition in Mozambique and a Potentially Missed Diagnosis in Women Presenting with Eclampsia.

PMID: 31681909 [PubMed]

PMCID: PMC6824723

EC Microbiology
Molecular Detection of Leptospira spp. in Rodents Trapped in the Mozambique Island City, Nampula Province, Mozambique.

PMID: 31681910 [PubMed]

PMCID: PMC6824726

EC Neurology
Endoplasmic Reticulum-Mitochondrial Cross-Talk in Neurodegenerative and Eye Diseases.

PMID: 31528859 [PubMed]

PMCID: PMC6746603

EC Psychology and Psychiatry
Can Chronic Consumption of Caffeine by Increasing D2/D3 Receptors Offer Benefit to Carriers of the DRD2 A1 Allele in Cocaine Abuse?

PMID: 31276119 [PubMed]

PMCID: PMC6604646

EC Anaesthesia
Real Time Locating Systems and sustainability of Perioperative Efficiency of Anesthesiologists.

PMID: 31406965 [PubMed]

PMCID: PMC6690616

EC Pharmacology and Toxicology
A Pilot STEM Curriculum Designed to Teach High School Students Concepts in Biochemical Engineering and Pharmacology.

PMID: 31517314 [PubMed]

PMCID: PMC6741290

EC Pharmacology and Toxicology
Toxic Mechanisms Underlying Motor Activity Changes Induced by a Mixture of Lead, Arsenic and Manganese.

PMID: 31633124 [PubMed]

PMCID: PMC6800226

EC Neurology
Research Volunteers' Attitudes Toward Chronic Fatigue Syndrome and Myalgic Encephalomyelitis.

PMID: 29662969 [PubMed]

PMCID: PMC5898812

EC Pharmacology and Toxicology
Hyperbaric Oxygen Therapy for Alzheimer's Disease.

PMID: 30215058 [PubMed]

PMCID: PMC6133268

News and Events

August Issue Release

We always feel pleasure to share our updates with you all. Here, notifying you that we have successfully released the August issue of respective journals and the latest articles can be viewed on the current issue pages.

Submission Deadline for Upcoming Issue

ECronicon delightfully welcomes all the authors around the globe for effective collaboration with an article submission for the upcoming issue of respective journals. Submissions are accepted on/before August 18, 2022.

Certificate of Publication

ECronicon honors with a "Publication Certificate" to the corresponding author by including the names of co-authors as a token of appreciation for publishing the work with our respective journals.

Best Article of the Issue

Editors of respective journals will always be very much interested in electing one Best Article after each issue release. The authors of the selected article will be honored with a "Best Article of the Issue" certificate.

Certifying for Review

ECronicon certifies the Editors for their first review done towards the assigned article of the respective journals.

Latest Articles

The latest articles will be updated immediately on the articles in press page of the respective journals.