Ocular Hypertension and Glaucoma: A Review and Current Perspectives
International Journal of Ophthalmology & Visual Science
Volume 2, Issue 2, May 2017, Pages: 22-36
Received: Mar. 7, 2017; Accepted: Mar. 27, 2017; Published: Apr. 14, 2017
Views 2018      Downloads 208
Najam A. Sharif, Global Alliances and External Research, Global Research & Development, Santen Incorporated, Emeryville, USA; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Texas Southern University, Houston, USA; Department of Pharmacology and Neuroscience, University of North Texas Health Sciences Center, Fort Worth, Texas, USA
Article Tools
Follow on us
Hypertension of the eye fundamentally results from an imbalance between the production and extrusion of aqueous humor (AQH) within the anterior segment of the eye. Vitreous humor (VH) (in the posterior segment of the eye) and AQH are responsible for maintaining the shape of the eye-ball in order that light is correctly focused on the retina for good vision. However, as we age, cells of the AQH drainage system (trabecular meshwork, TM) die and cellular debris accumulates within the TM and the canal of Schlemm thereby slowing, and in some cases, preventing AQH efflux. This results in increased resistance and elevation of hydrostatic pressure within the anterior segment, also termed as elevated intraocular pressure (IOP) or ocular hypertension (OHT). Sustained OHT exerts mechanical pressure on the retinal ganglion cells (RGCs) and the optic nerve fibers at the back of the eye leading to their progressive demise by apoptosis, thereby distorting and diminishing visual acuity over time, and eventually leading to irreversible blindness. In some patients even “normal” IOP is destructive because their RGCs and their axons projecting to the brain are genetically or chemically predisposed to early cell death. These pathologies are termed “glaucomatous optic neuropathy (GON)” and OHT is often associated with glaucoma, especially primary open-angle glaucoma (POAG). Today, there are several pharmacological and minimally invasive surgical interventions / devices that constitute therapeutic modalities to treat OHT and glaucoma. OHT etiology and treatments will be discussed in more detail in this review article.
Glaucoma, Ocular Hypertension, Neuroprotection, Pharmacology, Aqueous Humor
To cite this article
Najam A. Sharif, Ocular Hypertension and Glaucoma: A Review and Current Perspectives, International Journal of Ophthalmology & Visual Science. Vol. 2, No. 2, 2017, pp. 22-36. doi: 10.11648/j.ijovs.20170202.11
Copyright © 2017 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Civan M, Macknight AD. The ins and outs of aqueous humor secretion. Exp Eye Res. 2004; 78: 625-631.
Sacca SC, Pulliero A, Izzotti A. The dysfunction of the trabecular meshwork during glaucoma course. J Cell Physiol. 2015; 230: 510-525.
Coleman AL. Glaucoma. Lancet 1999; 354: 1803-1810.
Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet 2004; 363: 1711-1720.
Quigley HA. Glaucoma. 2011. Lancet 377: 1367-1377.
Sivak JM. The aging eye: common degenerative mechanisms between the Alzheimer’s brain and retinal disease. Invest Ophthalmol Vis Sci. 2013; 54: 871-880.
McKinnon SJ. The cell and molecular biology of glaucoma: common neurodegenerative pathways and relevance to glaucoma. Invest Ophthalmol Vis Sci. 2012; 53: 2485-2487.
Peters JC, Bhattacharya S, Clark AF, Zode GS. Increased endoplasmic reticulum stress in human glaucomatous trabecular meshwork cells and tissues. Invest Ophthalmol Vis Sci. 2015; 56: 3860-3868.
Casson RJ, Chidlow G, Wood JPM, Crowston JG, Goldberg I. Definition of glaucoma: clinical and experimental concepts. Clin Expt Ophthalmol. 2012; 40: 341-349.
Overby DR, Clark AF. Animal models of glucocorticoid-induced glaucoma. Exp Eye Res. 2015; 141: 1126-1130.
Gerometta R, Podos SM, Candia OA, Wu B. et al. Steroid-induced ocular hypertension in normal cattle. Arch Ophthalmol. 2004; 122: 1492-1497.
Gelatt KN, Brooks DE, Samuelson DA. Comparative glaucomatology, II: the experimental glaucomas. J Glaucoma 1998; 7: 282-294.
Congdon N, O’Colmain B, Klaver CC, Klein R, Munoz B, Friedman DS, Kempen J, Taylor HR, Mitchell P. Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol. 2004; 122: 477-485.
Tham Y-C, Li X, Wong TY, Quigley HA, Aung T, Cheng C-Y. Global prevalence of glaucoma and projections of glaucoma burden through 2040. Ophthalmol. 2014; 121: 2081-2090.
Aung T, Khor CC. Glaucoma Genetics: recent advances and future directions. Asia Pacific J Ophthalmol. 2016 (in press).
Borras T. Advances in glaucoma treatment and management: gene therapy. Invest Ophthalmol Vis Sci. 2012; 53: 2506-2510.
Bhattacharya SK, Lee RK, Grus FH et al. Molecular biomarkers in glaucoma. Invest Ophthalmol Vis Sci. 2013; 54: 121-131.
Williams PA, Harder JM, Foxworth NE, Cochran KE, Philip VM, Porciatti V, Smithies O, John SWM. Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice. Science 2017; 355: 756-760.
Clark AF, Yorio T. Ophthalmic drug discovery. Nature Rev Drug Discov. 2003; 2: 448-459.
Sharif NA, Klimko P. CNS: Ophthalmic Agents, in Comprehensive Medicinal Chemistry II., 2007; Vol. 6, Chapter 12, p. 297-320 (Eds: J. B. Taylor & D. J. Triggle), Elsevier, Oxford.
Bucolo C, Salomone S, Drago F, Reibaldie M, Longo A, Uva MG. Pharmacological management of ocular hypertension: current approaches and future prospectives. Curr Opin Pharmacol. 2013; 13: 50-55.
Chen J, Runyan SA, Robinson MR. Novel ocular antihypertensive compounds in clinical trials. Clin Ophthalmol. 2011; 5: 667-677.
Toris CB. Pharmacotherapies for glaucoma. Curr Mol Med. 2010; 10: 824-840.
Coleman AL. Advances in glaucoma treatment and management: surgery. Invest Ophthalmol Vis Sci. 2012; 53: 2491-2494.
Francis BA, Singh K, Lin SC, Hodapp E, Jampel HD, Samples JR, Smith SD. Novel glaucoma procedures. A report by the American Academy of Ophthalmology. Ophthalmol. 2011; 118: 1466-1480.
Rekas M, Danielewska ME, Byszewska A, Petz K, Wierzbowska J, Wierzbowska R, Iskander DR. Assessing efficacy of canaloplasty using continuous 24-hour monitoring of ocular dimensional changes. Invest Ophthalmol Vis Sci. 2016; 57: 2533-2542.
Richter GM, Coleman AL. Minimally invasive glaucoma surgery: current status and future prospects. Clin. Ophthalmol. 2016; 10: 189-206.
Manasses DT, AU L. The new era of glaucoma micro-stent surgery. Ophthalmol Ther. 2016; DOI 10.1007/s40123-016-0054-6.
Batlle JF, Fantes F, Riss I, Pinchuk L, Alburquerque R, Kato YP, Arrieta E, Peralta AC, Palmberg P, Parrish RK, Weber BA, Parel J-M. Three-year follow-up of a novel aqueous humor microshunt. J Glaucoma 2016; 25: 58-65.
SooHoo JR, Seibold LK, Radcliffe NM, Kahook MY. Minimally invasive glaucoma surgery: current implants and future innovations. Can J Ophthalmol. 2014; 49: 528-533.
Ferguson TJ, Berdahl JP, Schweitzer JA, Sudhagoni R. Evaluation of a trabecular micro-bypass stent in pseudophakic patients with open-angle glaucoma. J Glaucoma 2016; 25: 896-900.
Burgoyne CF, Downs JC, Bellezza AJ, Suh J-KF, Hart RT. 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. Prog Retinal Eye Res. 2005; 24: 39-73.
Hollander H, Makarov F, Stefani FH, Stone J. Evidence of constriction of optic axons at the lamina cribrosa in the normotensive eye in humans and other mammals. Ophthalmic Res. 1995; 27: 296-309.
Broadway DC, Drance SM. Glaucoma and vasospasm. Br J Ophthalmol. 1998; 82, 862-870.
Cull G, Told R, Burgoyne CF, Thompson S, Firtune B, Wang L. Compromized optic nerve blood flow and autoregulation secondary to neural degeneration. Invest Ophthalmol Vis Sci. 2015; 56: 7286-7292.
Flammer J, Orgul S. Optic nerve blood-flow abnormalities in glaucoma. Prog Retin Eye Res. 1998; 17: 267-289.
Park SC, Brumm J, Furlanetto RL, Netto C, Liu Y, Tello C, Liebmann JM, Ritch R. Lamina cribosa depth in different stages of glaucoma. Invest Ophthalmol Vis Sci. 2015; 56: 2059-2064.
Pasquale LR. Vascular and autonomic dysfunction in primary open-angle glaucoma. Curr Opin Ophthalmol. 2016; 27: 94-101.
Park H-Y L, Lee K-II, Lee K, Shin HY, Park CK. Torsion of the optic nerve head is a prominent feature of normal-tension glaucoma. Invest Ophthalmol Vis Sci. 2015; 156-163.
Girard MJA, Tun TA, Husain R, Acharyya S, Haaland BA, Wei X, Mari JM, Perera SA, Baskan M, Aung T, Strouthidis NG. Lamina cribosa visibility using optical coherence tomography: comparision of devices and effects of image enhancement techniques. Invest Ophthalmol Vis Sci. 2015; 56: 865-874.
Kim T-W, Kagemann L, Girard MJA, Strouthidis NG, Sung KR, Leung CK, Schuman JS, Wollstein G. Imaging of the lamina cribrosa in glaucoma: perspectives of pathogenesis and clinical applications. Curr Eye Res. 2013; 38: 903-909.
Sigal IA, Wang B, Strouthidis NG, Akagi T, Girard MJA. Recent advances in OCT imaging of the lamina cribrosa. Br J Ophthalmol. 2014; 98: ii34-ii39.
Bradley JM, Kelley MJ, Zhu X, Anderson AM, Alexander JP, Acott TS. Effects of mechanical stretching on trabecular matrix metalloproteinases. Invest. Ophthalmol. Vis. Sci. 2001; 42: 15015-1513.
Downs JC, Roberts MD, Sigal IA. Glaucomatous cupping of the lamina cribrosa: a review of the evidence for active progressive remodeling as a mechanism. Exp Eye Res. 2011; 93: 133-140.
Kanakamedala P, Harris A, Sierky B, Tyring A, Muchnik M, Eckert G, Tobe LA. Optic nerve head morphology in glaucoma patients of African descent is strongly correlated to retinal blood flow. Br J Ophthalmol. 2014; 98: 1551-1554.
Shiga Y, Omodaka K, Kunikata H, Ryu M, Tsuda S, et al. Waveform analysis of ocular blood flow and the early detection of normal tension glaucoma. Invest Ophthalmol Vis Sci. 2013; 54: 7699-7706.
Thomas D, Papadopoulo O, Doshi R, Kapin MA, Sharif NA. Retinal ATP and phosphorus metabolites: reduction by hypoxia and recovery with MK-801 and diltiazem. Med Sci Res. 2000; 28: 87-91.
Tezel G. Oxidative stress in glaucomatous neurodegeneration: mechanisms and consequences. Prog Retina Eye Res. 2006; 25: 490-513.
McElnea EM, Quill B, Docherty NG et al., Oxidative stress, mitochondrial dysfunction and calcium overload in human lamina cribrosa cells from glaucoma donors. Mol Vis. 2011; 17: 1182-1191.
Osborne NN, Nunez-Alvarez C, Joglar B, Del Olmo-Aguado S. Glaucoma: focus on mitochondria in relation to pathogenesis and neuroprotection. Eur J Pharmacol. 2016; 787: 127-133.
Coughlin L, Morrison RS, Horner PJ, Inman DM. Mitochondrial morphology differences and mitophagy deficits in murine glaucomatous optic nerve. Invest Ophthalmol Vis Sci. 2015; 56: 1437-1446.
Calkins DJ, Horner PJ. The cell and molecular biology of glaucoma: axonopathy and the brain. Invest Ophthalmol Vis Sci. 2012; 53: 2482-2484.
Prassana G, Krishnamoorthy R, Yorio T. 2011. Endothelin, astrocytes and glaucoma. Exp Eye Res. 2011; 93: 170-177.
Von Zee CL, Langert KA, Stubbs EB. Transforming growth factor-β2 induces synthesis and secretion of endothelin-1 in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2012; 53: 5279-5286.
Levin LA. Extrapolation of animal models of optic nerve injury to clinical trial design. J Glaucoma 2004; 13: 1-5.
Levin LA. Animal and cell culture models of glaucoma for studying neuroprotection. Eur J Ophthalmol. 2001; 11 (Suppl 2): S23-S29.
Chintala SK, Putris N, Geno M. Activation of TLR3 promotes the degeneration of retinal ganglion cells by upregulating the protein levels of JNK3. Invest Ophthalmol Vis Sci. 2015; 56: 505-514.
Nickell RW, Howell GR, Soto I, John SWM. Under pressure: cellular and molecular responses during glaucoma, a common neurodegeneration with axonopathy. Ann Rev Neurosci. 2012; 35: 153-179.
O’Hare F, Rance G, McKenrick AM, Crowston JG. Is primary open-angle glaucoma part of a generalized sensory neurodegeneration? A review of the evidence. Clin Expt Ophthalmol. 2012; 40: 895-905.
Pfeiffer N, Lamparter J, Gericke A, Grus FH, Hoffmann EM, Wahl J. Neuroprotection of medical IOP-lowering therapy. Cell Tissue Res. 2013; 353: 245-251.
Pease ME, McKinnon SJ, Quigley HA, Kerrigan-Baumrind LA, Zack DJ. Obstructed axonal transport of BDNF and its receptor TrkB in experimental glaucoma. Invest Ophthalmol Vis Sci. 2000; 41: 764-774.
Martinez-del-La-Casa J, Cifuentes-Conorea P, Berrozpe C, Sastre M, Polo V, Moreno-Montanes J, Garcia-Feijoo J. Diagnostic ability of macular nerve fiber layer thickness using new segmentation software in glaucoma suspects. Invest Ophthalmol Vis Sci. 2014; 55: 8343-8348.
Musch DC, Gillespie BW, Lichter PR, Niziol LM, Janz NK. Visual field progression in the Collaborative Initial Glaucoma Treatment Study: the impact of treatment and other baseline factors. Ophthalmol. 2009; 116: 200-207.
Caprioli J, Coleman AL. Intraocular pressure fluctuation a risk factor for visual field progression at low intraocular pressures in the advanced glaucoma intervention study. Ophthalmol. 2008; 115: 1123-129.e3.
Chen MF, Chui TYP, Alhadeff P, Rosen RB, Ritch R, Dubra A, Hood DC. Adaptic optic imaging of healthy and abnormal regions of retinal nerve fiber bundles of patients with glaucoma. Invest Ophthalmol Vis Sci. 2015; 56, 674-681.
Yang H, Lockwood H, Williams G, Libertiaux V, Downs C, Gardiner SK, Burgoyne CF. The connective tissue components of optic nerve head cupping in monkey experimental glaucoma part 1: global change. Invest Ophthalmol Vis Sci. 2015; 56: 7661-7678.
Krizaj D, Ryskamp DA, Tian N, Tezel G, Mitchell CH, Slepak VZ, Shestopalov VI. From mechanosensitivity to inflammatoryr responses: new players in the pathology of glaucoma. Curr Eye Res. 2013; 39:105-19.
Quigley HA, Dunklberger GR, Green WR. Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. Am J Ophthalmol. 1989; 107: 453-464.
Sponsel WE, Growth SL, Satangi N, Maddess T, Reilly MA. Refined data analysis provides clinical evidence for central nervous system control of chronic glaucomatous neurodegeneration. Trans Vis Sci Tech. 2014; 3: 1-13.
Yucel YH, Zhang Q, Gupta N, Kaufman PL, Weinreb RN. Loss of neurons in magnocellular and parvocellular layers of the lateral geniculate nucleus in glaucoma. Arch Ophthalmol. 2000; 118: 378-384.
Berdahl JP, Allingham RR, Johnson DH. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmol. 2008; 115: 763-768.
Wostyn P, De Groot V, Van Dam D, Audenaert K, Esriel K, De Deyn P. Glaucoma and the role of cerebrospinal fluid dynamics. Invest Ophthalmol Vis Sci. 2015; 56: 6630-6631.
Beidoe G, Mousa S. Current primary open-angle glaucoma treatments and future directions. Clin Ophthalmol. 2012; 6: 1699-1707.
Koutsonas A, Walter P, Roessler G, Plange N. Implantation of a novel telemetric intraocular pressure sensor in patients with glaucoma (ARGOS Study): 1-year results. Invest Ophthalmol Vis Sci. 2015: 56: 1063-1069.
Resende AF, Yung ES, Waisbourd M, Katz LJ. Monitoring intraocular pressure in glaucoma: current recommendations and emerging cutting-edge technologies. Expert Rev Ophthalmol. 2015; 10: 563-76.
Collaborative Normal-Tension Glaucoma Study Group. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol. 1998; 126, 498-505.
Mallick J, Devi L, Malik P, Mallick J. Update on normal tension glaucoma. J Ophthalmic Vis Res. 2016; 11: 204-208.
Kersey T, Clement C, Bloom P, Cordeiro MF. New trends in glaucoma risk, diagnosis and management. Ind J Med Res. 2013; 137: 659-668.
Kaufman PL, Rasmussen CA. Advances in glaucoma treatment and management: outflow drugs. Invest Ophthalmol Vis Sci. 2012; 53: 2495-2500.
Jonas JB. Role of cerebrospinal fluid pressure in the pathogenesis of glaucoma. Acta Ophthalmologica 2011; 89: 505-514.
Ammar DA, Hamweyah K, Kahook MY. 2012. Antioxidants protect trabecular meshwork cells from hydrogen peroxide-induced cell death. Trans Vis Sci Tech. 1(1):4.
Drace C, Williams G, Kelly CR, Sharif NA. Methods for treating glaucoma comprising administering α–lipoic acid. US Patent 2010; 7718697.
Melena J, Stanton D, Osborne NN. Comparative effects of antiglaucoma drugs on voltage?dependent calcium channels. Graefes Arch Clin Exp Ophthalmol 2001; 239:522?530.
Mayama C. Calcium channels and their blockers in intraocular pressure and glaucoma. Eur J Pharmacol. 2014; 739: 96-105.
Noro T, Namekata K, Azuchi Y, Kimura A, Guo X, Harade C, Nakano T, Tsuneoka H, Harada T. Spermidine ameliorates neurodegeneration in a mouse model of normal tension glaucoma. Invest Ophthalmol Vis Sci. 2015: 56: 5012-5019.
Sharif NA, Xu SX. Human retina contains polyamine-sensitive [3H]-ifenprodil binding sites: implications for neuroprotection? Br J. Ophthalmol. 1999; 83, 236-240.
Chang EE, Goldberg JL. Glaucoma 2.0: neuroprotection, neuroregeneration, neuroenhancement. Ophthalmol. 2012; 119, 979-986.
Gupta SK, Agarwal R, Galpalli ND, Srivasta S, Agrawal SS, Saxena R. Comparative efficacy of pilocarpine, timolol and latanoprost in experimental models of glaucoma. Meth Find Exp Clin Pharmacol. 2007; 29: 665-671.
Desantis L. Preclinical overview of brinzolamide. Surv Ophthalmol. 2000; (Supp. 2), S119-S129.
Sharif NA, Xu SX, Crider JY, McLaughlin M, Davis TL. Levobetaxolol (Betaxon?) and other ?–adrenergic antagonists: preclinical pharmacology, IOP-lowering activity and sites of action in human eyes.. J. Ocular Pharmacol Ther. 2001; 17: 305-317.
Sharif NA, Xu SX. Binding affinities of ocular hypotensive ?-blockers levobetaxolol, levobunolol and timolol at endogenous guinea pig ?–adrenoceptors. J. Ocular Pharmacol Ther. 2004; 20: 93-99.
Osborne SA, Montgomery DM, Morris D, McKay IC. Alphagan allergy may increase the propensity for multiple eye-drop allergy. Eye, 2005; 19: 129-137.
Hellberg MR, McLaughlin MA, Sharif NA, DeSantis L, et al. 2002. 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. Surv. Ophthalmol. 2002; (Suppl #1). 47: S13-S33.
Camras CB, Sharif NA, Wax MB, Stjernshantz J. Bimatoprost, the prodrug of a prostaglandin analogue. Br J. Ophthalmol. 2008; 92: 862-863.
Sharif NA, Klimko P. Update and commentary on the prodrug bimatoprost and a putative prostamide receptor. Expert Rev Ophthalmol.; 2009; 4: 477-489.
Sharif NA, Kelly CR, Crider JY. Human trabecular meshwork cell responses induced by bimatoprost, travoprost, unoprostone, and other FP prostaglandin receptor agonist analogues. Invest. Ophthalmol. Vis. Sci. 2003; 44: 715-721.
Kopczynski CC, Epstein DL. Emerging trabecular outflow drugs. J Ocular Pharmacol Ther., 2014; 30: 85-87.
Henderson AJ, Hadden M, Guo C, Douglas N, Decornez H, Hellberg MR, Rusinko A, McLaughlin M, Sharif NA, Drace C, Patil R. 2,3-Diaminopyrines as rho kinase inhibitors. Bioorgan Med Chem Lett. 2010; 20: 1137-1140.
Ramachandran C, Patil RV, Combrink K, Sharif NA, Srinivas SP. Rho-Rho kinase pathway in the actomyosin contraction and cell-matrix adhesion in immortalized human trabecular meshwork cells. Mol Vision 2011; 17: 1877-1890.
Cavet M, Vittitow JL, Impagnatello F, Ongini E, Bastia E. Nitric oxide (NO): an emerging target for the treatment of glaucoma. Invest Ophthalmol Vis Sci. 2014; 55: 5005-5015.
Medeiros FA, Martin KR, Peace J, Sforzolini BS, Vittitow JL, Weinreb RN. Comparison of Latanoprostene Bunod 0.024% and Timolol Maleate 0.5% in open-angle glaucoma or ocular hypertension: The LUNAR Study. Am J Ophthalmol. 2016; 168: 250–259.
Myers JS, Sall KN, Dubnier H, McVicar W, Rich C, Baumgartner RA. A dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of 2 and 4 weeks of twice-daily ocular trabodenoson in adults with ocular hypertension or primary open-angle glaucoma. J Ocular Pharmacol Ther. 2016; 32: 555-562.
Baiza-Duran LM, Alvarez-Delgado J, Contreras-Rubio AY, Medrano-Palafox J, De Luca-Brown A, Casab-Rueda H., et al. 2009. The efficacy and safety of two-fixed combinations: timolol-dorzolamide-brimonidine versus timolol-dorzolamide. A prospective, randomized, double-masked, multicenter, 6-month clinical trial. Ann Ophthalmol. 41: 174-178.
Hollo G, Topouzis F, Fechtner RD. Fixed-combination intraocular pressure-lowering therapy for glaucoma and ocular hypertension: advantages in clinical practice. Expert Opin Pharmacother. 2014; 15: 1737-1747.
Ellis D, Scheibler L, Sharif NA. Prostaglandin conjugates and derivatives for treating glaucoma and ocular hypertension. 2016; US Patent Appl. 0108012 A1.
Johnson TV, Tomarev SI. Rodent models of glaucoma. Brain Res Bull. 2010; 81: 349-358.
Sharif NA, McLaughlin MA, Kelly CR, Katoli P, Drace C, et al. Cabergoline: pharmacology, ocular hypotensive studies in multiple species, and aqueous humor dynamic modulation in Cynomolgus monkey eyes. Exp Eye Res. 2009; 88: 386-397.
Yan Z, Tian Z, Chen H, Deng S, Lin J, Liao H, Yang X, Zhuo Y. Analysis of a method establishing a model with more stable chronic glaucoma in rhesus monkeys. Exp Eye Res. 2015; 131, 56-62.
Fingert JH, Clark AF, Craig JE, Alward WL, Snibson GR, McLaughlin MA, Tuttle L, Mackay DA, et al. Evaluation of the myocilin (MYOC) glaucoma gene in monkey and human steroid-induced ocular hypertension. Invest Ophthalmol Vis Sci. 2001; 42: 145-152.
Kirihara T, Iwamura R, Yoneda K, Kawabata-Odani N, Shimazaki A, Kawazu K. DE-117, a selective EP2 agonist, lowered intraocular pressure in animal models. Invest Ophthal Vis Sci. 2015; 56: 5709.
Cordeiro MF, Guo L, Luong V, Harding G, Wang W, Jones HE, Moss SE, Sillito AM, Fitzke FW. Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration. Proc Natl Acad Sci USA 2004; 101:13352–13356.
Mayordomo-Febrer A, Lopez-Murcia, Morales-Tatay JM, Monleon-Salvado D. Metabolomics of the aqueous humor in the rat glaucoma model induced by a series of intracamerular sodium hyaluronate injection. Exp Eye Res. 2015; 131: 84-92.
Chowdhury UR, Madden BJ, Charlesworth MC, Fautch MP. 2010. Proteome analysis of human aqueous humor. Invest Ophthalmol Vis Sci. 51: 4921-4931.
Todani A, Behlau I, Fava MA, Cade F, Cherfan DG, Zakka FR, Jakobiec FA, Gao Y, Dohlman CH, Melki SA. Intraocular pressure measurement by radio wave telemetry. Invest Ophthalmol Vis Sci. 2011; 52:9573-80.
Zhu H, Crabb DP, Ho T, Garway-Heath GF. More accurate modeling of visual field progression in glaucoma: ANSWERS. Invest Ophthalmol Vis Sci. 2015; 56: 6077-6083.
Dismuke WM, Sharif NA, Ellis DZ. Human trabecular meshwork cell volume decrease by NO-independent soluble guanylate cyclase activators YC-1 and BAY-58-2667 involves the BKCa ion channel. Invest. Ophthalmol Vis Sci. 2009; 50: 3353-3359.
Dismuke WM, Sharif NA, Ellis DZ. Endogenous regulation of human Schlemm’s canal cell volume by nitric oxide signaling. Invest. Ophthalmol Vis Sci. 2010; 51: 5817-5824.
Salvi A, Bankhele P, Jamil J, Kulkarni-Chitnis M, Njie-Mbye Y-F, Ohia SE, Opere CA. Effect of hydrogen sulfide donors on intraocular pressure in rabbits. J. Ocular Pharmacol. Ther. 2016; 32: 371-375.
Ge P, Navarro ID, Kessler MM, Bernier SG, Perl NR, Sarno R, Masferrer J, Hannig G, Stamer DW. The soluble guanylate cyclase stimulator IWP-953 increases conventional outflow facility in mouse eye. Invest Ophthalmol Vis Sci. 2016; 57: 1317-1326.
Prasanna G, Fortner J, Xiang C, Zhang E, Carreiro S, Anderson S, Sartnurak S, Wu G, Gukasyan H, Niesman M, Nair S, Rui E, Lafontaine J, Almaden CD, Wells P, Krauss A. Ocular pharmacokinetics and hypotensive activity of PF-04475270, an EP4 prostaglandin agonist in preclinical models. Exp Eye Res. 2009; 89: 608-17.
Sharif NA, Williams GW, Crider JY, Xu SX, Davis TL. Molecular pharmacology of the ocular hypotensive DP/EP2 class prostaglandin AL-6598 and localization of DP and EP2 receptor sites in human eyes. J. Ocular Pharmacol. Ther. 2004; 20: 489-508.
Prasanna G, Carreiro S, Anderson S, Gukasyan H, Sartnurak S,Younis H, Gale D, Xiang C, Wells P, Dinh D, Almaden S, Fortner J, Toris C, Niesman M, Lafontaine J, Krauss A. Effect of PF-04217329 a prodrug of a selective prostaglandin EP2 agonist on intraocular pressure in preclinical models of glaucoma. Exp Eye Res. 2011; 93: 256-264.
Ihekoromadu N, Lu F, Iwamura R, Yoneda K, Kawabata-Odani N, Shams NK. Safety and Efficacy of DE-117, a Selective EP2 Agonist in a Phase 2a Study. Invest Ophthal Vis Sci. 2015; 56: 5708.
May JA, Dantanarayana AP, Zinke PW, McLaughlin MA, Sharif NA. 1-((S)-2-Aminopropyl)-1H-indazol-6-ol: A potent peripherally acting 5 HT2 receptor agonist with ocular hypotensive activity. J. Med. Chem. 2006; 49: 318-328.
Sharif NA, McLaughlin MA, Kelly CR. AL-34662: a potent, selective, and efficacious ocular hypotensive serotonin-2 receptor agonist. J. Ocular Pharmacol. Ther. 2007; 23: 1-13.
May JA, Sharif NA, McLaughlin MA, Chen H-H, Severns BS, Kelly CR, Holt WF, Young R, Glennon RA, Hellberg, MR, Dean TR. Ocular hypotensive response in non-human primates of (R)-1-((S)-2-Aminopropyl)-1,7,8,9-tetrahydro-pyrano[2,3-g]indazol-8-ol a selective 5-HT2 receptor agonist. J. Med. Chem. 2015; 58: 8818-8833.
Suto F, Rowe-Rendleman CL, Ouchi T, Jamil A, Wood A, Ward CL. A novel dual agonist of EP3 and FP receptors for OAG and OHT: safety, pharmacokinetics, and pharmacodynamics of ONO-9054 in healthy volunteers. Invest Ophthalmol. Vis Sci. 2015; 56: 7963-7970.
Yamane S, Karakawa T, Nakayama S, Nagai K, Moriyuki K, Neki S, Suto F, Kambe T, Kawabata K. IOP-lowering effect of ONO-9054, a novel dual agonist of prostanoid EP3 and FP receptors, in monkeys. Invest Ophthalmol Vis Sci. 2015; 56: 2547-2552.
Wang RF, Podos SM, Mittag TW, Yokoyoma T. Effect of CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure in glaucomatous monkey eyes. Exp Eye Res. 2005: 80: 629-632.
Vaajanen A, Vapaatalo H, Kautiainen H, Oksala O. 2008. Angiotensin (1-7) reduces intraocular pressure in the normotensive rabbit eye. Invest Ophthalmol Vis Sci. 2008; 49: 2557-25662.
Foureaux G, Nogueira JC, Nogueira BS, Fulgencio GO, Menezes GB, Fernandes SOA et al. Antiglaucomatous effects of the activation of intrinsic angiotensin-converting enzyme 2. Invest Ophthalmol Vis Sci. 2013; 54: 4296-4306.
Agarwal R, Krasilnikova AK, Safinaz RI, Agarwal P, Ismail NM. Mechanisms of angiotensin converting enzyme inhibitor-induced IOP reduction in normotensive rats. Eur J Pharmacol. 2014; 730: 8-13.
Holappa M, Vapaatalo H, Vaajanen A. Ocular renin-angiotensin system with special reference to the anterior part of the eye. W J Ophthalmol. 2015; 5: 110-124.
Ma JX, Song Q, Hatcher HC, Crouch RK, Chao L, Chao J. Expression and cellular localization of the kallikrein-kinin system in human ocular tissues. Exp Eye Res. 1996; 63: 19-26.
Sharif NA, Xu SX. Pharmacological characterization of bradykinin receptors coupled to phosphoinositide turnover in SV40 immortalized human trabecular meshwork cells. Exp Eye Res. 1996; 63: 631-637.
Webb JG, Husain S, Yates PW, Crosson CE. Kinin modulation of conventional outflow facility in bovine eye. J Ocular Pharmacol Ther. 2006; 22: 310-316.
Webb JG, Yang X, Crosson CE. Expression of the kallikrein/kinin system in human anterior segment. Exp Eye Res. 2009; 89: 126-132.
Webb JG, Yang X, Crosson CE. Bradykinin activation of extracellular signal-regulated kinases in human trabecular meshwork cells. Exp Eye Res. 2011; 92: 495-501.
Sharif NA. Use of non-peptidic bradykinin receptor agonists to treat ocular hypertension and glaucoma. US Patent 2012; 8173668.
Combrink K, Mohapatra S, Hellberg MR, Sharif NA, Prasanna G, et al. Bradykinin receptor agonists and uses thereof to treat ocular hypertension and glaucoma. US Patent 2012; 8252793.
Prasanna G, Sharif NA, Li B, Hellberg M, Krause T, Yacoub S, Scott D, Kelly C, Pang IH, Combrink K. BK2A78: a novel non-peptide bradykinin B2 agonist lowers intraocular pressure (IOP) in ocular hypertensive Cynomolgus monkeys. Assoc Res Vis Ophthalmol. 2014; Abst. # 2883.
Sharif NA, Xu S, Li L, Katoli P, Kelly C, Wang Y, Cao S, Patil R, Klekar L, Scott D, Husain S. Protein expression, biochemical pharmacology of signal transduction, and relation to IOP modulation by bradykinin B2-receptors in ciliary muscle. Mol Vision 2013; 19: 1356-1370.
Sharif NA, Wang Y, Katoli P, Xu S, Kelly CR, Li L. Human non-pigmented ciliary epithelium bradykinin B2-receptors: receptor localization, pharmacological characterization of intracellular Ca2+ mobilization, and prostaglandin secretion. Curr Eye Res. 2014; 39: 378-389.
Sharif NA, Katoli P, Kelly CR, Li L, Xu S, Wang Y, Klekar L, Earnest D, Yacoub S, Hamilton G, Jacobson N, Shepard AR, Ellis D. Trabecular meshwork bradykinin receptors: mRNA levels, immunohistochemical visualization, signaling processes pharmacology and linkage to IOP changes. J. Ocular Pharmacol Ther. 2014; 30: 21-34.
Sharif NA, Li L, Peng Y, Katoli P, Xu S, Veltman J, Li B, Scott D, Wax M, Gallar J, Acosta C, Belmonte C. Preclinical pharmacology, ocular tolerability and ocular hypotensive efficacy of a novel non-peptide bradykinin mimetic small molecule. Exp Eye Res. 2014; 128: 170-180.
Sharif NA, Katoli P, Scott D, Li L, Kelly CR, Xu S, Husain S, Toris C, Crosson C. FR-190997, a non-peptide bradykinin B2-receptor partial agonist, is a potent and efficacious intraocular pressure lowering agent in ocular hypertensive cynomolgus monkeys. Drug Develop Res. 2014; 75: 211-223.
Whitcup SM. Clinical trials in neuroprotection. Prog Brain Res. 2008; 173: 323-335.
Neufeld AH, Kawai SI, Das S, Vora S, Gachie E, Connor JR, et al. Loss of retinal ganglion cells following retinal ischemia: The role of inducible nitric oxide synthase. Exp Eye Res 2002; 75: 521?528.
Wood JP, DeSantis L, Chao HM, Osborne NN. Topically applied betaxolol attenuates ischemia-induced effects to the rat retina and stimulates BDNF mRNA. Exp Eye Res. 2001; 72, 79-86.
Gao H, Qiao X, Cantor LB, WuDunn D. Up-regulation of brain-derived neurotrophic factor expression by brimonidine in rat retinal ganglion cells. Arch. Ophthalmol. 2002; 120: 797-803.
Chadder GJ. Advances in glaucoma treatment and management: neurotrophic agents. Invest Ophthalmol Vis Sci. 2012; 53: 2501-2505.
Saylor M, McLoon LK, Harrison AR, Lee MS. Experimental and clinical evidence for brimonidine as an optic nerve and retinal neuroprotective agent: an evidence-based review. Arch Ophthalmol. 2009; 12: 402-406.
Krupin T, Liebmann JM, Greenfield DS, Ritch R, Gardiner S. A randomized trial of brimonidine versus timolol in preserving visual function: results from the Low-Pressure Glaucoma Treatment Study. Am J Ophthalmol. 2011; 151: 671-681.
Osborne NN, Cazervielle C, Carvalho AL, Larsen AK, DeSantis L. In vivo and in vitro experiments show that betaxolol is retinal neuroprotective agent. Brain Res. 1997; 751: 113-123.
Agarwal N, Martin E, Krishnamoorthy RR, Landers R, Wen R, Krueger S, Kapin MA, Collier RJ. Levobetaxolol-induced Up-regulation of retinal bFGF and CNTF mRNAs and preservation of retinal function against a photic-induced retinopathy. Exp Eye Res. 2002; 74: 445-53.
Abdul Y, Akhter N, Husain S. Delta opioid agonist SNC-121 protects retinal ganglion cell function in a chronic ocular hypertensive rat model. Invest Ophthalmol Vis Sci. 2013; 54: 1816-1828.
Burgess LG, Uppal K, Walker DI, Roberson RM, Tran V, Parks MB, Wade EA, May AT, Umfress AC, Jarrell KL, Stanley BOC, Kuchtey J, Jones DP, Brantley MA. Metabolome-wide association study of primary open angle glaucoma. Invest Ophthalmol Vis Sci. 2015; 56: 5020-5028.
Wiederholt M, Thieme H, Stumpff F. The regulation of trabecular meshwork and ciliary muscle contractility. Prog. Retinal Eye Res. 2000; 19: 271-295.
Chowdhury UR, Hann CR, Stamer DW, Fautsch MP. Aquoeus humor outflow: dynamics and disease. Invest Ophthalmol Vis Sci. 2015; 56: 2993-3003.
Tam ALC, Gupta N, Zhang Z, Yucel YH. Latanoprost stimulates ocular lymphatic drainage: an in vivo nanotracer study. Trans Vis Sci Tech. 2013; 2 (5): 3.
Liu JHK, Slight JR, Vittitow JL, Sforzolini BS, Weinreb RN. Efficacy of Latanoprostene Bunod 0.024% compared with Timolol 0.5% in lowering intraocular pressure over 24 hours. AmJ Ophthalmol. 2016; 169: 249–257.
Luna C, Li G, Huang J, Qiu J, Wu J, Yuan F, Epsteins DL, Gonzalez P. Regulation of trabecular meshwork cell contraction and intraocular pressure by MiR-200c. PloS One 2012; 7: 251688.
Johnson TV, Martin KR. Cell transplantation approaches to retinal ganglion cell neuroprotection in glaucoma. Curr Opin Pharmacol. 2013; 13: 78?82.
Chamling X, Sluch SM, Zack DJ. The potential of human stem cells for the study and treatment of glaucoma. Invest Ophthalmol Vis Sci. 2016; 57: ORSFi1–ORSFi6.
Harrison BA, Whitlock NA, Voronkov MV, Almstead ZY, Gu K-J, Allen J, Gopinathan S, et al. Novel class of LIM-kinase inhibitors for the treatment of ocular hypertension and associated glaucoma. J Med Chem. 2009; 52: 6515-6518.
Kirihara T, Shimazaki A, Nakamura M, Miyawaki N. Ocular hypotensive efficacy of Src-family tyrosine kinase inhibitors via different cellular actions from Rock inhibitors. Exp Eye Res. 2014; 119: 97-105.
Takashima Y, Taniguchi T, Yoshida M, Haque MS, Igaki T, Itoh H, Nakao K, Honda Y, Yoshimura N. Ocular hypotension induced by intravitreally injected C-type natriuretic peptide. Exp Eye Res. 1998; 66: 89-96.
Potter DE, Russell KR, Manhiani M. Bremazocine increases C-type natriuretic peptide levels in aqueous humor and enhances outflow facility. J Pharmacol Exp Ther. 2004; 309: 548-553.
Novack GD. Cannabinoids for treatment of glaucoma. Curr Opin Ophthalmol. 2016; 27: 146-150.
Faulkner R, Sharif NA, Orr S, Craven R, Moster M, Sall K, Whitson J, Bethem R, Curtis M, Dahlin D. Aqueous humor concentrations of bimatoprost free acid, bimatoprost and travoprost free acid in cataract surgical patients administered multiple topical ocular doses of LUMIGAN? or TRAVATAN?. J. Ocular Pharmacol Ther. 2010; 26: 147-156.
Chiou GC, Li B. Ocular hypotensive actions of serotonin antagonist-ketanserin analogs. J Ocular Pharmacol. 1992; 8: 11-21.
Civan MM. The fall and rise of active chloride transport: implications for regulation of intraocular pressure. J Exp Zool A Comp Exp Biol. 2003; 300: 5-13.
Katz A, Tal DM, Heller D, Habeck M, Ben Zeev E, Rabah B, Bar Kana Y, Marcovich AL, Karlish SJD. Digoxin derivatives with selectivity for the isoform of Na+,K+-ATPase potently reduce intraocular pressure. Proc Nat Acad. Sci. (USA) 2016; 112: 13723-13728.
Ogidigben MJ, Potter DE. Comparative effects of alpha-2 and DA-2 agonists on intraocular pressure in pigmented and nonpigmented rabbits. J Ocul Pharmacol. 1993; 9:187-99.
Tanna AP, Rademaker AW, Stewart WC, Feldman RM. Meta-analysis of the efficacy and safety of alpha2-adrenergic agonists, beta-adrenergic antagonists, and topical carbonic anhydrase inhibitors with prostaglandin analogs. Arch Ophthalmol. 2010; 128: 825-33.
Chidlow G, DeSantis LM, Sharif NA, Osborne NN. The characteristics of [3H] 5 hydroxytrytamine binding to iris ciliary body of the rabbit. Invest. Ophthalmol. Vis Sci. 1995; 36: 2238 2245.
Chidlow G, Nash MS, DeSantis L, Osborne NN. The 5-HT1A Receptor agonist 8-OH-DPAT lowers intraocular pressure in normotensive NZW rabbits. Exp Eye Res. 1999; 69: 587-593.
Sharif NA. Novel potential treatment modalities for ocular hypertension: focus on angiotensin and bradykinin system axes. J. Ocular Pharmacol Ther. 2015; 31: 131-145.
Sharif NA, Patil R, Li L, Husain S. Human ciliary muscle cell responses to kinins: activation of ERK1/2 and pro-matrix metalloproteinases secretion. World J. Ophthalmol. 2016; 6: 20-27.
Patil R, Xu S, Rusinko A, Feng Z, Katoli P, May JA, Hellberg M, Sharif NA, Wax M, Irigoyen M, Clarke M, et al. Rapid identification of novel inhibitors of aquaporin-1 channel by high-throughput screening. Chem. Biol Drug Design 2016; 87: 794-805.
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186