Nitric Oxide Synthase Inhibitors Exert Differential Time-Dependent Effects on LPS-Induced Uveitis

Allen, Julie K.; McGahan, M.C.; Ferrell, J.; Adler, Kenneth B.; Fleisher, Lloyd N.

doi:10.1006/exer.1996.0003

Cited by 41 publications

(23 citation statements)

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“…Group IV was provoked by intravitreal injection of lipopolysaccharide (LPS) (10 ng/eye) (17). Group V was provoked by subconjunctival injection of NO donor S-nitroso-N-acetyl-D, L-penicillamine (SNAP) (50 M).…”

Section: The Role Of Nitric Oxide In Ocular Surface Cellsmentioning

confidence: 99%

The Role of Nitric Oxide in Ocular Surface Cells

et al. 2002

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The role of nitric oxide (NO) in the ocular surface remains unknown. We investigated the conditions leading to an increase of NO generation in tear and the main sources of NO in ocular surface tissue. We evaluated the dual action (cell survival or cell death) of NO depending on its amount. We measured the concentration of nitrite plus nitrate in the tears of ocular surface diseases and examined the main source of nitric oxide synthase (NOS). When cultured human corneal fibroblast were treated with NO producing donor with or without serum, the viabilities of cells was studied. We found that the main sources of NO in ocular surface tissue were corneal epithelium, fibroblast, endothelium, and inflammatory cells. Three forms of NOS (eNOS, bNOS, and iNOS) were expressed in experimentally induced inflammation. In the fibroblast culture system, the NO donor (SNAP, S-nitroso-N-acetyl-D, L-penicillamine) prevented the death of corneal fibroblast cells caused by serum deprivation in a dose dependent manner up to 500 micrometer SNAP, but a higher dose decreased cell viability. This study suggested that NO might act as a double-edged sword in ocular surface diseases depending on the degree of inflammation related with NO concentration.

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Section: The Role Of Nitric Oxide In Ocular Surface Cellsmentioning

confidence: 99%

The Role of Nitric Oxide in Ocular Surface Cells

et al. 2002

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“…The role of peroxynitrites in ocular inflammation is still largely unknown, although as highly reactive and potent oxidizers, these substances are shown to peroxidize lipids in the membranes. Characterization of the roles of these important uveitic mediators in the ocular inflammatory response will provide information crucial to the understanding of the pathogenesis of intraocular inflammation so that more effective therapeutic interventions can be developed [7,8].…”

Section: Discussionmentioning

confidence: 99%

Tear Nitrite and Nitrate Levels as Nitric Oxide End Products in Patients with Behçet’s Disease and Non-Behçet’s Uveitis

Karaküçük

et al. 2000

Ophthalmic Res

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To evaluate the role of nitric oxide (NO) in ocular inflammation, tear nitrite and nitrates (NN) as NO end products were determined in 11 patients with Behçet’s disease (BD) and in 11 with non-Behçet’s uveitis (NBU) during the active and remission stages and in 12 healthy controls. Median (with the range) NN levels were 82.29 (59.60–98.25) µmol/l in the active and 98.25 (52.88–246.92) µmol/l in the remission stage of BD; 88.17 (25.99–116.73) µmol/l in the active and 83.00 (31.04–250.28) µmol/l in the remission stage of NBU and 109.17 (88.17–158.74) µmol/l in the controls. The NN levels in the active stage of BD and NBU were significantly decreased when compared to the controls (p < 0.05; Kruskal-Wallis test). Decreased NN levels at the activation stage may be caused by the rapid transformation of the NO to peroxynitrites, which are highly oxidizing and cytotoxic substances.

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“…Several investigations using the endotoxin-induced uveitis (EIU) mouse and rat models document the importance of NO in ocular inflammation (57)(58)(59)(60)(61)(62)(63)(64)(65). Intraperitoneal injections of L-NAME, an inhibitor of both cNOS and iNOS, significantly decrease aqueous protein and cell numbers in the anterior chamber of EIU in rats (60).…”

Section: No and Onoo-in Experimental Uveitismentioning

confidence: 99%

“…In addition, prostaglandins and other mediators have been associated with uveitis. Studies using the EIU model in rabbits have documented a role for NO and ONOO-in ocular inflammation (65,70).…”

Section: No and Onoo-in Experimental Uveitismentioning

confidence: 99%

“…The eyes are removed and processed for histologic/molecular analyses. Hematoxylin and eosin-stained sections of eye, removed 18 In an attempt to dissect the importance and contribution of the different NOS isoforms in uveitis, the authors used the iNOS and cNOS (L-NAME; 100 mM and 10 mM) and iNOS (AG; 114 mM) inhibitors in EIU in rabbits (65). These and additional published studies underscore the importance of determining which NOS isoform(s) is important at various stages of the inflammatory process.…”

Section: No and Onoo-in Experimental Uveitismentioning

confidence: 99%

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Nitric oxide and peroxynitrite production in ocular inflammation.

Allen

Keng

Privalle

1998

Environ Health Perspect

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Recent studies have implicated nitric oxide and peroxynitrite in the pathogenesis of many diseases, such as septic shock, arthritis, lung disease, and atherosclerosis. Nitric oxide ('NO) exerts many diverse effects on vascular tone, affecting neurotransmission and cellular cytotoxicity/communication. Our laboratory and others have documented a proinflammatory role for 'NO in ocular inflammation. Uveitis, which is an inflammation of the highly vascular uveal tract in the eye, is a debilitating condition that can lead to visual impairment and blindness. It is characterized by acute, recurrent, or persistent inflammation with disruption of the blood-aqueous barrier and is accompanied by protein leakage and leukocyte infiltration into the aqueous humor and anterior chamber. Systemic injection of endotoxin into mice and rats, or intraocular injection of endotoxin into mice, rats, and rabbits induces acute uveitis, which clinically and histologically resembles acute anterior uveitis in humans. These models facilitate the study of pathogenic mechanisms that contribute to ocular inflammation. In addition to 'NO, superoxide anion radicals (02'-), and peroxynitrite (ONOO-), the products of the reaction between 'NO and 02'-, are also implicated in uveitis. The role of peroxynitrite in ocular inflammation is still largely unknown. Characterization of the roles of these important uveitic mediators in the ocular inflammatory response will provide information critical to the understanding of the pathogenesis of intraocular inflammation so that more effective therapeutic intervention(s) can be developed.

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Nitric Oxide Synthase Inhibitors Exert Differential Time-Dependent Effects on LPS-Induced Uveitis

Cited by 41 publications

References 0 publications

The Role of Nitric Oxide in Ocular Surface Cells

The Role of Nitric Oxide in Ocular Surface Cells

Tear Nitrite and Nitrate Levels as Nitric Oxide End Products in Patients with Behçet’s Disease and Non-Behçet’s Uveitis

Nitric oxide and peroxynitrite production in ocular inflammation.

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