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: Multiple biomarker panels of common, multifactorial diseases - such as cardiovascular and Alzheimer’s disease - have recently been described, facilitating the diagnosis and risk management of these diseases. In principle, a biomarker is an indicator of a biochemical feature or facet that can be used to diagnose or monitor the progress of a disease. Detection technology has been identified for possible types of biomarkers in primary open-angle glaucoma (POAG). We will summarize known biomarkers with the intent of cataloging the biomarkers in the aqueous humor, trabecular meshwork (TM), optic nerve, and blood in patients with POAG. To facilitate comparisons and to offer mechanistic clues, biochemical changes such as up- or downregulation of proteins that have been reported in POAG are organized into three categories: namely, extracellular matrix (ECM) changes, cytokine/signaling molecules, and aging/stress (listed respectively in Tables 82.1, 82.2, and 82.3).
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ABSTRACT: To determine the aqueous humor levels of nitric oxide (NO) and vascular endothelial growth factor (VEGF) in the eyes of patients with Coats' disease and study the correlation between these levels. Samples of aqueous humor were obtained from 7 patients with Coats' disease and 15 age-matched patients with congenital cataracts as controls. Nitrite and nitrate (NOx), the stable end products of NO, were detected by the Griess reaction, and VEGF levels were assessed by enzyme-linked immunosorbent assay. The aqueous humor NOx and VEGF levels were elevated in the eyes of patients with Coats' disease compared with those of controls (P=0.001 and P<0.001, respectively). The median NOx level was 55.2 μM (range, 23.0-75.3 μM) in the Coats' disease group and 18.8 μM (range, 8.7-36.2 μM) in the control group. The median VEGF level was 731.7 pg/mL (range, 288.3-1364.3 pg/mL) in the Coats' disease group and 33.3 pg/mL (range, 9.0-96.8 pg/mL) in the control group. No correlation was observed between the aqueous humor concentrations of NOx and VEGF. NOx and VEGF are increased but not related in the aqueous humor samples of patients with Coats' disease. NO and VEGF may play roles in the pathogenesis of Coats' disease. Further studies are needed to clearly elucidate the relationship among VEGF, NO, and other cytokines in Coats' disease.Journal of ocular pharmacology and therapeutics: the official journal of the Association for Ocular Pharmacology and Therapeutics 01/2012; 28(4):397-401. · 1.46 Impact Factor
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ABSTRACT: The rho-associated kinase (ROCK) signaling pathway is activated via secreted bioactive molecules or via integrin activation after extracellular matrix binding. These lead to polymerization of actin stress fibers and formation of focal adhesions. Accumulating evidence suggests that actin cytoskeleton-modulating signals are involved in aqueous outflow regulation. Aqueous humor contains various biologically active factors, some of which are elevated in glaucomatous eyes. These factors affect aqueous outflow, in part, through ROCK signaling modulation. Various drugs acting on the cytoskeleton have also been shown to increase aqueous outflow by acting directly on outflow tissue. In vivo animal studies have shown that the trabecular meshwork (TM) actin cytoskeleton in glaucomatous eyes is more disorganized and more randomly oriented than in non-glaucomatous control eyes. In a previous study, we introduced ROCK inhibitors as a potential glaucoma therapy by showing that a selective ROCK inhibitor significantly lowered rabbit IOP. Rho-associated kinase inhibitors directly affect the TM and Schlemm's canal (SC), differing from the target sight of other glaucoma drugs. The TM is affected earlier and more strongly than ciliary muscle cells by ROCK inhibitors, largely because of pharmacological affinity differences stemming from regulatory mechanisms. Additionally, ROCK inhibitors disrupt tight junctions, result in F-actin depolymerization, and modulate intracellular calcium level, effectively increasing SC-cell monolayer permeability. Perfusion of an enucleated eye with a ROCK inhibitor resulted in wider empty spaces in the juxtacanalicular (JCT) area and more giant vacuoles in the endothelial cells of SC, while the endothelial lining of SC was intact. Interestingly, ROCK inhibitors also increase retinal blood flow by relaxing vascular smooth muscle cells, directly protecting neurons against various stresses, while promoting wound healing. These additional effects may help slow progressing visual field loss in glaucoma patients, making ROCK inhibitors an even more desirable anti-glaucoma agent. All evidence indicates that aqueous humor outflow is affected by cytoskeleton physiology and this information may provide valuable insight into understanding glaucoma pathology and treatment.Progress in Retinal and Eye Research 06/2013; · 9.44 Impact Factor