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: The pressures in the episcleral veins, Schlemm's canal and the trabecular meshwork were studied with a micropuncture technique using cannulas with tip diameters of less than 5 microns. The pressure in Schlemm's canal, Psc, was 14.3 +/- 1.0 cmH2O at spontaneous intraocular pressure, IOP, 19.2 +/- 0.9 cmH2O. The outflow pressure from the anterior chamber to Schlemm's canal was 4.9 +/- 0.7 cmH2O. The relationship between pressures was IOP = 0.73 Psc + 8.7. When the intraocular pressure was increased stepwise from the spontaneous level to 30 cmH2O there was an increase in pressure in Schlemm's canal of 1.7 +/- 0.6 cmH2O, (P less than 0.05). The total outflow resistance and the resistance between the anterior chamber and Schlemm's canal were 3.27 +/- 0.43 and 2.92 +/- 0.50 cmH2O min microliter-1 respectively for the intraocular pressure interval between the spontaneous pressure and a level 4-11 cmH2O higher. In the intraocular pressure range from 20 to 30 cmH2O the corresponding figures were 2.89 +/- 0.45 and 2.69 +/- 0.42 cmH2O min microliter-1 and for the pressure range 25-35 cmH2O, 2.48 +/- 0.58 and 2.31 +/- 0.59 cmH2O min microliter-1. The difference between the total outflow resistance and that between the anterior chamber and Schlemm's canal was about 10% of the total at intraocular pressures below 35 cmH2O. Stepwise increments in IOP increased the trabecular meshwork pressure by 0.88 cmH2O for each cmH2O increase in IOP in the interval of 30-50 cmH2O. The total outflow resistance and the resistance between the anterior chamber and the tip of the microcannula was 3.91 +/- 1.53 and 1.94 +/- 0.99 cmH2O min microliter-1 respectively for the intraocular pressure interval between the spontaneous pressure and 30 cmH2O. In the interval between 30 and 45 cmH2O the corresponding figures were 2.16 +/- 0.66 and 0.20 +/- 0.13 cmH2O min microliter-1. The episcleral venous pressure at the spontaneous intraocular pressure was 14.1 +/- 1.0 cmH2O in seven animals with minimal trauma, and 12.3 +/- 0.8 cmH2O in animals after cannulation of Schlemm's canal. The outflow pressure from the anterior chamber to the episcleral veins was 4.4 +/- 1.2 cmH2O in animals with minimal trauma and 7.1 +/- 0.8 cmH2O after cannulation of Schlemm's canal. The relationship between pressures was IOP = 0.68EVP + 11.(ABSTRACT TRUNCATED AT 400 WORDS)Experimental Eye Research 11/1989; 49(4):645-63. · 3.03 Impact Factor
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ABSTRACT: The nitrovasodilators nitroglycerin (NTG) and hydralazine (HZN) were investigated for their effects on intraocular pressure (IOP) and outflow facility in the cynomolgus monkey eye in vivo. Fifty microliters of 0.1% HZN were administered topically in masked, randomized, crossover, placebo controlled trials, and by intracameral perfusion. Both NTG and HZN decreased IOP (mean IOP decrease with NTG 4.40 +/- 2.11 (S.E.M.) (+/- 4.7, S.D.) mmHg, P < 0.01, n = 5, with HZN 3.15 +/- 0.85 (S.E.M.) (+/- 2.3, S.D.) mmHg, P = 0.01, n = 7). Outflow facility increased by 92% (P < 0.05) after intracameral bolus injection of 10(-3) mol l-1 NTG, but not at lower doses. Intracameral HZN caused a significant increase in facility of outflow of 28% (P < 0.05) when perfused at a constant concentration of 10(-5) mol l-1, but not at certain other concentrations. These results demonstrate the capacity for topically applied NTG and HZN to reduce IOP in the living primate eye. They further suggest that, at certain drug doses, but not others, the IOP reduction may be mediated, in part, by an action on the outflow apparatus.Experimental Eye Research 01/1994; 58(1):99-105. · 3.03 Impact Factor
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ABSTRACT: Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia. We measured the concentration of VEGF in 210 specimens of ocular fluid obtained from 164 patients undergoing intraocular surgery, using both radioimmuno-assays and radioreceptor assays. Vitreous proliferative potential was measured with in vitro assays of the growth of retinal endothelial cells and with VEGF-neutralizing antibody. VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabetic retinopathy, 29 of 38 samples from patients with neovascularization of the iris, and 3 of 4 samples from patients with ischemic occlusion of the central retinal vein, as compared with 2 of 31 samples from patients with no neovascular disorders (P < 0.001, P < 0.001, and P = 0.006, respectively). The mean (+/- SD) VEGF concentration in 70 samples of ocular fluid from patients with active proliferative diabetic retinopathy (3.6 +/- 6.3 ng per milliliter) was higher than that in 25 samples from patients with nonproliferative diabetic retinopathy (0.1 +/- 0.1 ng per milliliter, P = 0.008), 41 samples from patients with quiescent proliferative diabetic retinopathy (0.2 +/- 0.6 ng per milliliter, P < 0.001), or 31 samples from nondiabetic patients (0.1 +/- 0.2 ng per milliliter, P = 0.003). Concentrations of VEGF in vitreous fluid (8.8 +/- 9.9 ng per milliliter) were higher than those in aqueous fluid (5.6 +/- 8.6 ng per milliliter, P = 0.033) in all 10 pairs of samples obtained simultaneously from the same patient; VEGF concentrations in vitreous fluid declined after successful laser photocoagulation. VEGF stimulated the growth of retinal endothelial cells in vitro, as did vitreous fluid containing measurable VEGF. Stimulation was inhibited by VEGF-neutralizing antibodies. Our data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.New England Journal of Medicine 01/1995; 331(22):1480-7. · 51.66 Impact Factor