Significant variation of the elevated nitric oxide levels in aqueous humor from patients with different types of glaucoma.
ABSTRACT Though several studies have shown that the biochemical function of nitric oxide (NO) in the eye might play an important role in the regulation of intraocular pressure (IOP), local control of ocular blood flow and loss of retinal ganglion cells by apoptosis, it is unclear whether the role of NO is similar in the pathogenesis of different kinds of glaucoma: primary open-angle glaucoma (POAG), chronic closed-angle glaucoma (CCAG) and neovascular glaucoma (NVG). To further explore this issue, we measured the concentrations of NO in aqueous humor and plasma samples from patients with POAG (n = 31), CCAG (n = 76), NVG (n = 8) and cataract (n = 30). All of the NVG patients suffered from severe proliferative diabetic retinopathy, while other patients were free of any other systemic disease. The NO levels in both aqueous humor and plasma samples were assessed by chemiluminescence assay. We found that the NO levels in aqueous humor samples were greatly varied in patients with POAG (36.2 +/- 3.3 microM), CCAG (47.7 +/- 3.4 microM) and NVG (65.8 +/- 5.4 microM), and all of them were significantly higher than in cataract patients (27.0 +/- 2.9 microM p < 0.05). Except NVG patients whose NO levels in plasma samples were highest (24.1 +/- 3.5 microM) among all groups, the plasma NO levels were not significantly different between the other glaucoma patients and the cataract patients. We therefore concluded that significant variation of the elevated NO levels in aqueous humor samples from the patients with different types of glaucoma may reflect their differences in the pathogenesis.
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ABSTRACT: Recent findings generated from our laboratory have demonstrated the involvement of nitric oxide (NO) in morphine-induced reduction of intraocular pressure (IOP). The present study was designed to investigate the possible involvement of carbon monoxide (CO) in morphine-induced reduction of IOP and the role of mu(3) opioid receptors. New Zealand rabbits were used in this study. They were pretreated with the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME, 1%, 30 microL), or an inhibitor of heme oxygenase (HO), zinc protoporphyrin-IX (ZnPP-IX; 0.1 mg/kg; i.v.). The same animals were then treated with morphine (100 microg/30 microL) with or without NO or CO donors administration, sodium nitroprusside (SNP) and tricarbonylchloro(glycinato)ruthenium(II) (CORM-3), respectively. A separate set of animals were pretreated with the nonselective opioid receptor antagonist, naloxone (100 microg/30 microL), or the micro(3) opioid receptor inhibitor, L-glutathione (GSH, 1%, 30 microL), in the presence of SNP or CORM-3 followed by morphine administration. IOP measurements were taken at different times after monolateral instillation of morphine. Morphine induced a significant decrease in IOP and pretreatment with ZnPP-IX or L-NAME significantly prevented this effect whereas administration of NO or CO donors amplified morphine-induced decrease in IOP. This effect was partially abrogated both by pretreatment with ZnPP-IX or L-NAME, and by pretreatment with naloxone and GSH suggesting that the decrease in IOP relies on exogenous NO and CO liberated from SNP and CORM-3, respectively. We conclude that the endogenous NO/CO system and micro(3) receptors contribute to morphine-induced ocular hypotension and that the reduction of IOP elicited by morphine can be augmented by exogenous NO and CO.Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 02/2010; 26(1):31-5. · 1.46 Impact Factor
Article: Neuroprotection in glaucoma.[Show abstract] [Hide abstract]
ABSTRACT: Glaucoma is a neurodegenerative disease characterized by loss of retinal ganglion cells and their axons. Recent evidence suggests that intraocular pressure (IOP) is only one of the many risk factors for this disease. Current treatment options for this disease have been limited to the reduction of IOP; however, it is clear now that the disease progression continues in many patients despite effective lowering of IOP. In the search for newer modalities in treating this disease, much data have emerged from experimental research the world over, suggesting various pathological processes involved in this disease and newer possible strategies to treat it. This review article looks into the current understanding of the pathophysiology of glaucoma, the importance of neuroprotection, the various possible pharmacological approaches for neuroprotection and evidence of current available medications.Indian Journal of Ophthalmology 01/2011; 59 Suppl:S102-13. · 1.02 Impact Factor
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ABSTRACT: To investigate the levels of endothelin-1 (ET-1) and nitric oxide (NO) in the aqueous humor and plasma of human eyes with different types of glaucoma: primary open-angle glaucoma (POAG) and chronic closed-angle glaucoma (CCAG). Patients were classified into 3 groups: group I comprised 35 patients with POAG, group II comprised 25 patients with CCAG, and 30 patients with senile cataract (group III) were used as a control group. Aqueous humor and corresponding plasma were analyzed for ET-1 and NO concentrations by enzyme-linked immunosorbent assay. A Bonferroni correction for multiple comparisons was performed. There was no significant difference in plasma levels of either ET-1 or NO metabolites between the groups studied. ET-1 and NO were significantly elevated in the aqueous humor of patients with CCAG and POAG compared to the corresponding value in patients with cataract (p < 0.001). ET-1 and NO concentrations in the aqueous humor were more marked in CCAG than in POAG. NO levels were correlated with ET-1 in the aqueous humor of patients with glaucoma (p < 0.001). Increased concentrations of ET-1 and NO in aqueous humor may be useful with POAG and CCAG. In addition, ET-1 and NO may have useful metabolite levels in the aqueous humor of POAG and CCAG patients as a result of glaucoma damage and may not be a cause of it.Ophthalmic Research 01/2011; 46(2):98-102. · 1.56 Impact Factor