Journal of Postgraduate Medicine
 Open access journal indexed with Index Medicus & EMBASE  
     Home | Subscribe | Feedback  

[Download PDF
Year : 2003  |  Volume : 49  |  Issue : 1  |  Page : 90-5  

Neuroprotection in glaucoma.

S Kaushik, SS Pandav, J Ram 
 Department of Ophthalmology, Postgraduate Institute of medical education and Research, Chandigarh-160 012, India., India

Correspondence Address:
S Kaushik
Department of Ophthalmology, Postgraduate Institute of medical education and Research, Chandigarh-160 012, India.


Currently, glaucoma is recognised as an optic neuropathy. Selective death of retinal ganglion cells (RGC) is the hallmark of glaucoma, which is also associated with structural changes in the optic nerve head. The process of RGC death is thought to be biphasic: a primary injury responsible for initiation of damage that is followed by a slower secondary degeneration related to noxious environment surrounding the degenerating cells. For example, retinal ishaemia may establish a cascade of changes that ultimately result in cell death: hypoxia leads to excitotoxic levels of glutamate, which cause a rise in intra-cellular calcium, which in turn, leads to neuronal death due to apoptosis or necrosis. Neuroprotection is a process that attempts to preserve the cells that were spared during the initial insult, but are still vulnerable to damage. Although not yet available, a neuroprotective agent would be of great use in arresting the progression of glaucoma. There is evidence that neuroprotection can be achieved both pharmacologically and immunologically. Pharmacological intervention aims at neutralising some of the effects of the nerve-derived toxic factors, thereby increasing the ability of the spared neurons to cope with stressful conditions. On the other hand, immunological interventions boost the body«SQ»s own repair mechanisms for counteracting the toxic effects of various chemicals generated during the cascade. This review, based on a literature search using MEDLINE, focuses on diverse cellular events associated with glaucomatous neurodegeneration, and discusses some pharmacological agents believed to have a neuroprotective role in glaucoma.

How to cite this article:
Kaushik S, Pandav S S, Ram J. Neuroprotection in glaucoma. J Postgrad Med 2003;49:90-5

How to cite this URL:
Kaushik S, Pandav S S, Ram J. Neuroprotection in glaucoma. J Postgrad Med [serial online] 2003 [cited 2023 Jun 3 ];49:90-5
Available from:

Full Text

Glaucoma associated with distinctive changes in the disc and visual fields, is viewed as an optic neuropathy characterized by progressive loss of retinal ganglion cells (RGC). This concept emphasizes that several pressure-independent mechanisms are responsible for the development and progression of glaucomatous neuropathy and that high intra-ocular pressure (IOP) and vascular insufficiency in the optic nerve head are merely risk factors for the development of glaucoma. The central role of raised IOP is being questioned as many patients continue to demonstrate a clinically downhill course despite control of initially raised IOP.[1] In addition, up to one-sixth of patients with glaucoma develop it despite normal IOP.[2] A great deal of research is being conducted for the development of neurotropic agents that would help prevent RGC death. In addition, researchers are also looking at induction of cell rescue mechanisms as an alternative strategy for neuroprotection. This review, based on an extensive literature search using MEDLINE, provides information about the pathophysiological aspects of glaucomatous optic nerve damage and the state of research regarding the development of neuroprotective and antiapoptotic agents.

In humans, the optic nerve consists of approximately one million axons; whose cell bodies are primarily located in the ganglion cell layer.[3] RGC death, therefore, represents the final common pathway of virtually all diseases of the optic nerve including glaucomatous optic neuropathy. There is histological and electrophysiological evidence to suggest that ganglion cells are the sole neurons affected in glaucoma,[3] while the remainder of the inner and outer retina remain uninvolved. The excavated appearance of the optic nerve head in glaucoma is thought to be caused by death of the ganglion cells and subsequent loss of their axons.[4] Electroretinogram (ERG) is normal in glaucoma, indicating normal photoreceptor and bipolar/Muller’s cells.[5] Histopathological studies have shown that, in glaucoma, retinal ganglion cells and axons die, while no other neurons are visibly affected.[6]

It is necessary to understand certain concepts about cell death before discussing the pathophysiology of glaucomatous optic neuropathy. It is now understood that most mammalian cells die through apoptosis, which is a complex active cellular process that results in an orderly self-destruction. It is also known that whatever the inciting insult or injury, actual cell death occurs through a final common pathway. In addition, Kerr et al[7] described the process of secondary degeneration wherein neuronal damage continues even when the primary cause of damage is ameliorated or eliminated. They suggested that healthy neurons suffer progressive damage due to their close proximity to the dying neurons as the former are exposed to the noxious environment created by the latter and subsequently suffer the same fate of cell death. Thus, neuronal death can be thought to occur in three stages: axonal injury, death of the injured neuron and injury to and death of the neighbouring intact neurons through secondary degeneration.

The excessive loss of neurons has been attributed to the delayed biochemical processes that lead to neuronal death in excess of that caused by the primary injury.[9],[10] It appears that, regardless of the primary lesion (ischaemia, hypoxia, stroke, mechanical trauma, degenerative neuronal disease), the damage to neurons leads to similar changes in the extra-cellular milieu: alteration in the ionic concentrations, increased amounts of free radicals, release of neurotransmitters, depletion of growth factors and alterations in the immune system.[11],[12] The hostile milieu, therefore, allows for a self-perpetuating destructive cascade that remains active long after the initial or primary insult has abated. The extent of succeeding degeneration, however, remains a function of the severity of the initial insult, i.e. more severe the primary insult, more extensive is the secondary degeneration.

Yoles and Schwartz[13] hypothesised that this concept provided a plausible explanation for two important clinical observations in glaucoma. First, in some cases, progression of glaucomatous damage continues despite attenuation of the initial insult, viz. high IOP. Secondly, patients with severe pre-existing damage are more likely to deteriorate despite having the same or even lower IOPs than those who do not have visual field loss at the time of diagnosis. Neufield[14] described a model concept of the internal milieu of a glaucomatous eye as having RGCs in various conditions ranging from normal, sick, degenerating and dead. The fate of these cells is a function of their proximity to the original site of damage, coupled with individual susceptibility.

The strategy of treating a disease by preventing neuronal death is termed neuroprotection. The term is used more narrowly to describe therapies to address final common pathways of damage in many neurological diseases ranging from amyotrophic lateral sclerosis, Alzheimer’s disease and, in the context of the eye, glaucoma. The potential role of neuroprotective agents is to rescue of sick and dying cells and to maintain the integrity of healthy cells by providing resilience to a variety of hostile factors or agents.

  ::   Mechanisms of retinal ganglion cell deathTop

Research into the actual events leading to the death of RGCs has delineated several mechanisms that may be responsible for RGC death:

1. Neurotrophin withdrawal due to retrograde axoplasmic transport block.

2. Glutamate induced excitotoxicity.

3. Free radical generation

4. Nitric oxide neurotoxicity

5. Apoptosis

Neurotrophin Withdrawal

The neurotrophic hypothesis holds that mammalian neuronal growth and maintenance depend upon the viability of retrograde axoplasmic transport of soluble growth factors called neurotrophins.[15] The neurotrophins supplied to the RGCs are small peptides that function to regulate cellular metabolism by attaching themselves to neuronal target-cell receptors. From there, they initiate a cascade of molecular enzymatic events and maintain cellular homeostasis. Ganglion cells appear to be particularly dependent upon the brain-derived neurotrophin factor (BDNF) which is necessary for their continued survival.[16],[17]. This factor can promote survival and prevent neuronal death after axotomy in the optic nerve.[18] Further support for the neurotrophic hypothesis comes from the findings of Gao et al[19] who showed an enhanced expression of BDNF in the RGC layer after optic nerve injury.

Glutamate Induced Excitotoxicity

Glutamate is the main excitatory neurotransmitter in the central nervous system and is present in neurons in very high concentrations. Glutamate induced excitotoxicity occurs when extra-cellular glutamate levels are increased, either due to increased release or decreased uptake from the synapse. High glutamate concentrations activate several types of cell receptors, including N-methyl-D-aspartate (NMDA) receptors that can allow entry of excessive amounts of calcium. Abnormally high Ca2+ concentration leads to inappropriate activation of complex cascades of nucleases, proteases and lipases. They directly attack cell constituents and lead to the generation of highly reactive free radicals and activation of the nitric oxide pathway.[20] The resulting interaction between intermediate compounds and free radicals leads to DNA nitrosylation, fragmentation and activation of the apoptotic programme.

Free Radical Generation

Free radicals are generated not only through the activation of glutamate receptors but also as an inevitable by-product of normal oxidative mechanisms.[21] This is especially true in the retina which has a very high metabolic rate. Endogenous antioxidants such as superoxide dismutase, Vitamins E and C, and glutathione normally inactivate these free radicals. However, when not inactivated sufficiently, they can react detrimentally with most macromolecular cellular constituents and may lead to protein conversion, lipid peroxidation and nucleic acid breakdown.

Nitric Oxide Neurotoxicity

Nitric oxide neurotoxicity occurs through the reaction of nitric oxide with superoxide anion to form peroxynitrite and other more reactive free radical species. Peroxynitrite acts by S-nitrosylating both proteins and nucleic acids, thus destroying them.[22]


All animal cells are programmed for carrying out self-destruction when they are not needed, or when damaged. Apoptosis is a process rather than an event. It has been labelled a programmed cell death, or cell suicide. It is not unique to RGCs or glaucoma alone. Following an initial insult, the cells try to minimize or buffer the damage done through a variety of processes. Generation of “suicide triggers” could be one of the consequences of these processes and interactions and these molecules may start the process of apoptosis which is characterized by an orderly pattern of inter-nucleosomal DNA fragmentation, chromosome clumping, cell shrinkage and membrane blebbing.[22] This is followed by disassembly of cells into multiple membrane-enclosed vesicles, that are engulfed by neighbouring cells without inciting inflammation. Cell death with apoptosis is often contrasted with death by necrosis. Necrosis is classically marked by cellular swelling, disruption of organelle and plasma membranes, random DNA fragmentation, and uncontrolled release of cellular constituents into extra-cellular space usually resulting in inflammation.

  ::   NeuroprotectionTop

The objective of neuroprotective therapy is to employ pharmacologic or other means to attenuate the hostility of the environment or to supply the cells with the tools to deal with these changes.[23] According to this approach, any chronic degenerative disease may be viewed to have, at any given time, some neurons undergoing an active process of degeneration which contributes to the hostility of the environment surrounding it. The exponential loss of cells after secondary degeneration stems from the damage brought on other neurons that either escaped or were only marginally damaged by the primary injury.[24] Neuroprotection attempts to provide protection to such neurons that continue to remain at risk.[25]

The inherent attractiveness of neuroprotection lies in absence of the need to treat the cause of the disease. Regardless of whether pressure-dependent or pressure-independent factors are at work, neuroprotection attempts to address the final common pathway of a variety of insults leading to RGC death.

  ::   Neuroprotective agentsTop

The loss of RGCs in glaucoma appears progressively over many years. A neuroprotective drug should enhance the survival of RGCs in the presence of chronic stress/injury. Wheeler and WoldeMussie[26] proposed four criteria to assess the likely therapeutic utility of neuroprotective drugs with demonstrated utility in animal studies: The drug should have a specific receptor target in the retina/ optic nerve; activation of the target must trigger pathways that enhance a neuron’s resistance to stress or must suppress toxic insults, the drug must reach the retina/ vitreous in pharmacologically effective concentrations and the neuroprotective activity must be demonstrated in clinical trials.

A host of pharmacological drugs, growth factors, and other compounds have been reported to be neuroprotective in vitro, and in a number of neurologic and neurodegenerative disorders. Numerous clinical trials in stroke, Parkinsonism and Alzheimer’s disease are underway at the present time. However, no clinical trials of neuroprotection in glaucoma have yet been reported. Nevertheless, the variety of biochemical processes taking place present potential avenues for neuroprotective intervention. Some of the agents reported to have neuroprotective activity in the optic nerve are presented.

Ca2+ channel blockers (CCB): They have been shown to neutralize glutamate-NMDA-induced intracellular Ca2+ influx. In a retrospective study of normal-tension and open-angle glaucoma patients who happened to be taking calcium channel blockers, Netland et al[27] demonstrated a decrease in glaucoma progression relative to controls. Kittazawa et al[28] suggested visual improvement in a significant number of patients who took nifedipine in a 6-month prospective study. Flunarizine, a potent CCB has been demonstrated to enhance RGC survival after optic nerve transection in mice.[29] Although seemingly beneficial, one concern is that the blood-pressure lowering properties that make them useful in cardiovascular diseases might also decrease perfusion in the optic nerve and result in further ischemia.[30]

Antiglaucoma medications: Betaxolol is thought to possess some calcium-channel blocking activity, which could explain tis apparent vasodilating activity. [31] Additionally, Gross et al [32] have shown that it exerts actions on the retinal ganglion cells by reversibly blocking glutamate-gated currents and subsequent firing of ganglion cells. Recently, Brimonidine has been demonstrated to have neuroprotective attributes by virtue of its ability to reduce the rate of RGC loss in a rat optic nerve injury model.[24] Gao et al[33] also demonstrated that intra-vitreal brimonidine significantly increased endogenous BDNF expression in rat RGCs. A clinical trial has been instituted to determine brimonidine’s neuroprotective activity in patients with non-arteritic ischaemic neuropathy.

NMDA Antagonists: NMDA antagonists can inhibit over-stimulation of the NMDA receptor, which then provides neuroprotection by preventing excessive calcium influx. One NMDA antagonist, memantine, is presently undergoing testing in a placebo-controlled prospective, randomised, multi-centric trial in the US. Memantine effectively blocks the excitotoxic response of retinal ganglion cells both in culture and in vivo.[34] In a rat model of retinal ischemia created by elevating IOP to 120 mm Hg, memantine reduced ganglion cell loss when given systemically.[35]

Antioxidants: Antioxidants neutralise other suicide triggers such as reactive oxygen species emanating from the glutamate cascade. Free radical scavengers like catalase, superoxide dismutase, and vitamins C and E are useful for mopping up loose by-products generated during secondary degeneration.

Nitric Oxide synthase (NOS-2) inhibitors: NO in significant amounts plays a significant role in DNA nitrosylation and fragmentation that precedes apoptosis.[20] Neufield et al[36] examined the use of oral aminoguanidine, an inhibitor of NOS-2, for its effect in preventing glaucomatous cupping in a rat model created by cauterising three episcleral vessels. After 6 months of treatment, the optic nerve heads of the untreated animals had pallor and cupping, while those of the treated animals appeared normal. In histological specimens, the untreated eyes had lost a mean of 36% of their retinal ganglion cells, whereas those in the treated group had lost less than 10%.

Neurotrophins: Neurotrophic support through endogenous and exogenous sources is being evaluated. BDNF, ciliary neurotrophin factor, and basic fibroblastic growth factor have been shown to promote human retinal ganglion cell survival in culture and in vivo.[37] One suggested approach is to deliver these substances by creation of a fistula between the anterior chamber and vitreous cavity through which neurotrophins from the iris can reach the retina.

Ginkgo biloba extract (GBE): This is freely available as a nutritional supplement in the US. It is claimed to be effective in a variety of disorders associated with ageing, including cerebrovascular disease, peripheral vascular disease, dementia, tinnitus, bronchoconstricition and sexual dysfunction.[38] GBE exerts protective effects against free radical damage and lipid peroxidation in various tissue and experimental systems. It preserves mitochondrial metabolism and ATP production in various tissues. It is also a scavenger of superoxide radicals and nitric oxide.[39]

GBE has been found to improve both peripheral and cerebral blood flow. In one clinical study by Chung et al,[40] it was demonstrated that low-dose, short-term treatment with GBE in healthy volunteers, increased ophthalmic artery blood flow by a mean of 24%.

  ::   Ideal drug for the treatment of glaucomaTop

The ideal anti-glaucoma drug would be one that prevents ganglion cell death and has no adverse effects on the patient. Should the patient also have increased IOP, this can be treated separately.[41] However, in reality, any drug targeted specifically to the retina to prevent ganglion cell death is likely to have appreciable side effects. Therefore, at the present time, a more realistic ideal drug would be one that when applied topically, reduces IOP, and reaches the retina in appropriate amounts to attenuate retinal ganglion cell death.

  ::   Gene therapy: future possibilitiesTop

Intense research in gene therapy has made it an emerging therapeutic possibility in glaucoma management. Advances in the expression of apoptosis-involved genes or their protein products have demonstrated neuroprotective capacity in vitro. Several gene families have been identified that play either positive or negative roles in determining whether a cell will undergo apoptosis. Caspases are cysteine proteins that both propagate apoptotic signals as well as carry out disassembly of the cell.[42] Many triggers activate caspases including increased intracellular calcium, free radicals and adenosine 3’5'- cyclic phosphate.[43] The prototype of the mammalian caspase is interleukin-1b converting enzyme (ICE).

The main inhibitors of apoptosis are Bcl-2 and related proteins. They have multiple complex functions, such as inhibiting intermediate proteins that activate caspases.[44] One of the primary regulatory steps in apoptosis is the activation of tumour suppression protein, p53.[45] This protein functions as a transcription factor that can up-regulate the expression of the pro-apoptotic gene bax and down-regulate the expression of the anti-apoptotic gene bcl-2.

Martinou et al[46] have successfully generated a transgenic mouse line that allowed expression of the apoptosis-inhibiting gene Bcl-2 in rat neurons. The result was a 50% increase in retinal ganglion cell numbers accompanied by an increase in the thickness of the inner plexiform layer. Deprenyl, a monoamine oxidase inhibitor used in Parkinson’s disease, is an example of a compound capable of increasing gene expression that inhibits apoptosis. Other promising compounds include flunarizine and aurintricarboxylic acid, which apparently delay apoptosis after light-induced photoreceptor cell death.[47]

An understanding of the genetic pathways of apoptosis may lead to the design of new treatments that could prevent its activation or arrest the process when started. A gene could be delivered to the relevant tissue via several possible mechanisms including viruses, artificial liposomes, and direct transfer. Alternatively, one could induce the cell to express the requisite gene by its own regulatory pathways. Ultimately, gene therapy could replace the mutant gene with a normal one before visual loss has occurred.


1Brubaker RF. Delayed functional loss in glaucoma. LII Edward Jackson Memorial Lecture. Am J Ophthalmol 1996;121:473-83.
2Lisegang TJ. Glaucoma: changing concepts and future directions. Mayo Clin Proc 19967;689-94.
3Osborne NN, Ugarte M, Chao M, Chidlow G, Bae JH, Wood JP, et al. Neuroprotection in relation to retinal ischemia and relevance to glaucoma. Surv Ophthalmol 1999;43(Suppl):102-28.
4Quigley HA, Green WR. The histology of human glaucoma cupping and optic nerve damage: clinicopathologic correlation in 21 eyes. Ophthalmology 1979;86:1803-30.
5Korth M, Horn F, Stork B, Jonas J. The pattern evoked electroretinogram: age related alterations and changes in glaucoma. Graefes Arch Clin Exp Ophthalmol 1989;227:123-30.
6Quigley HA, Addicks EM, Green WR, Maumenee AE. Optic nerve damage in human glaucoma II. The site of injury and susceptibility to damage. Arch Ophthalmol 1981;99:635-49.
7Wein FB, Levin LA. Current understanding of neuroprotection in glaucoma. Curr Opin Ophthalmol 2002;13:61-7.
8Kerr JF, Wyilie AH, Currle AR. Apoptosis: a basic biologic phenomenon with wide-ranging complications in tissue kinetics. Br J Cancer 1972;26:239-57.
9Faden AI. Pharmacotherapy in spinal cord injury: a critical review of recent developments. Clin Neuropharmacol 1987;10:193-204.
10Lynch DR, Dawson TM. Secondary mechanisms in neuronal trauma. Curr Opin Neurol 1994;7:510-6.
11Choi DA. Glutamate neurotoxicity and diseases of the nervous system. Neuron 1988;1:623-34.
12Siesjo BK. Mechanisms of ischaemic brain damage. Crit Care Med 1988;16:954-63.
13Yoles E, Schwartz M. Potential neuroprotective therapy for glaucomatous optic neuropathy. Surv Ophthalmol 1998;42:367-72.
14Neufield AH. New conceptual approaches for pharmacological neuroprotection in glaucomatous neuronal degeneration. J Glaucoma 1998;7:434-8.
15Mckinnon SJ. Glaucoma, apoptosis and neuroprotection. Curr Opin Ophthalmol 1997;8:28-37.
16Nickells RW. Retinal ganglion cell death in glaucoma: the how, the witty and the maybe. J Glaucoma 1996;5:345-56.
17Nickells RW, Zack DJ. Apoptosis in ocular disease: a molecular review. Ophthalmic Genet 1996;17:145-65.
18Quigley HA, Nickells RW, Kerrigan LA, Pease ME, Thibault DJ, Zach DJ. Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest Ophthalmol Vi Sci 1995;36:774-86.
19Gao H, Qiaou X, Hefti F, Holyfield JG, Knusel B. Elevated mRNA expression of brain-derived neurotrophic factor in retinal ganglion cell layer after optic nerve injury. Invest Ophthalmol Vis Sci 1997;38:1840-7.
20Naskar R, Dreyer EB. New horizons in neuroprotection. Surv Ophthlamol 2001;45(Suppl 3):S250-6.
21Boveris A, Chance B. The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 1973;134:707-16.
22Farkas RH, Grosskreutz CL. Apoptosis, neuroprotection and retinal ganglion cell death: An overview. Int Ophthalmol Clin 2001;41:111-30.
23Kaufman PL, Gabelt BT, Cynader M. Introductory comments on neuroprotection. Surv Ophthalmol 1999;43(Suppl):S89-90.
24Schwartz M, Belkin M, Yoles E, Solomon A. Potential treatment modalities for glaucomatous neuropathy: neuroprotection and neuroregeneration. J Glaucoma 1996;5:427-32.
25Chew SJ, Ritch R. Neuroprotection: the next break through in glaucoma? Proceedings of the third Annual Optic Nerve Rescue and Restoration Think Tank. J Glaucoma 1997;6:263-66.
26Wheeler LA, Gil DW, WoldeMussie E. Role of alpha-2 adrenergic receptors in neuroprotection and glaucoma. Surv Ophthalmol 2001;45(Suppl)3:S290-6.
27Netland PA, Chaturvedi N, Dreyer EB. Calcium channel blockers in the management of low tension and open angle glaucoma. Am J Ophthalmol 1993;115:608-13.
28Kittazawa Y, Shirai H, Go FJ. The effect of ca2+ antagonist on visual field in low-tension glaucoma. Graefes Arch Clin Exp Ophthalmol 1989;227:408-12.
29Eschweiler GW, Bahr M. Flunarizine enhances rat retinal ganglion cell survival after axotomy. J Neurol Sci 1993;116:34-40.
30Caprioli J. Neuroprotection of the optic nerve in glaucoma. Acta Ophthalmol Scand 1997;75:364-7.
31Bautista RD. Glaucomatous neurodegeneration and the concept of neuroprotection. Int Ophthalmol Clin 1999;39:57-70.
32Gross RL, Hensley SH, Gao F, Wu SM. Retinal ganglion cell dysfunction induced by hypoxia and glutamate: potential neuroprotective effects of beta-blockers. Surv Ophthalmol 1999;43(Suppl 1):S162-70
33Gao H, Qiao X, Cantour LB, Wu Dunn D. Up-regulation of brain-derived neurotrophic factor expression by brimonidine in rat retinal ganglion cells. Arch Ophthalmol 2002;120:797-803.
34Vorwerk CK, Lipton SA, Zurakowski D, Hyman BT, Sobel BA, Dreyer EB. Chronic low-dose glutamate is toxic to retinal ganglion cells: toxicity blocked by memantine. Invest Ophthalmol Vis Sci 1996;37:1618-24.
35Lagreze WA, Knorle R, Bach M, Feuerstein TJ. Memantine is neuroprotective in a rat model of pressure-induced retinal ischemia. Invest Ophthalmol Vis Sci 1998;39:1063-6.
36Neufeld AH, Sawada A, Becker B. Inhibition of nitric oxide synthase-2 by aminoguanidine provides neuroprotection of retinal ganglion cells in a rat model of chronic glaucoma. Proc Nat Acad Sci USA 1999;96:9944-8.
37Rabacchi SA, Ensini M, Bonfanti I, Grarina A, Maffei L. Nerve growth factor reduces apoptosis of axotomized retinal ganglion cells in the neonatal rat. Neuroscience 1994;63:969-73.
38Ritch R. Neuroprotection: Is it already applicable to glaucoma therapy? Curr Opin Ophthalmol 2000;11:78-84.
39Janssens D, Michiels C, Delaive E, Eliaers F, Drieu K, Remacle J. Protection of hypoxia induced ATP decrease in endothelial cells by Ginkgo biloba extract and bilobalide. Biochem Pharmacol 1995;50:991-9.
40Chung HS, Harris A, Kristinsson JK, Ciulla TA, Kagemann C, Ritch R. Ginkgo biloba extract increased ocular blood flow velocity. J Ocul Pharmacol Ther 1999;15:233-40.
41Sood NN, Sood D. Primary glaucomas: current concepts and management. J Indian Med Assoc 2000;98:763-7.
42Hetts SW. To die or not to die: an overview of apoptosis and its role in disease. JAMA 1998;279:300-7.
43GarrielI Y, Sherman Y, Ben-Sasson SA. Identification of programmed cell-death in situ via labeling of nuclear DNA fragmentation. J Cell Biol 1992;119:493-501.
44Adams JM, Cory S. The Bcl-2 functions in an antioxidant pathway to prevent apoptosis. Science 1998;281:1322-6.
45Nickells RW. Apoptosis of retinal ganglion cells in glaucoma: an update of the molecular pathways involved in cell death. Surv Ophthalmol 1999;43:S151-61.
46Martinou JC, Dubois-Dauphin M, Staple JK, Rodriguez I, Frankowski M, Missotten M, et al. Overexpression of Bcl-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 1994;13:1017-30.
47Lam TT, Fu J, Hyrnewycz M, Tso MO. The effect of aurintricarboxylic acid, an endonuclease inhibitor, on ischemia/ reperfusion damages in rat retina. J Ocular Pharmacol Ther 1995;11:253-9.

Saturday, June 3, 2023
 Site Map | Home | Contact Us | Feedback | Copyright  and disclaimer