Role of nitric oxide (NO) in ocular inflammation

Abstract

The actions of nitric oxide (NO) have been investigated in the rabbit eye, with particular emphasis on the relationship between NO and C‐fibres and on those effects of NO that may be of importance in the inflammatory response to C‐fibre stimulation. The NO synthase inhibitor, NG‐nitro‐L‐arginine (L‐NAME; 10–200 mg kg−1), but not the inactive analogue D‐NAME (200 mg kg−1), was found to block the inflammatory response induced by infrared irradiation of the iris in a dose‐dependent manner. The inhibitory effects of L‐NAME (200 mg kg−1) were partially reversed by L‐arginine (500 mg kg−1), but not by D‐arginine (500 mg kg−1). L‐NAME (200 mg kg−1) virtually abolished the ocular effects of intravitreal injection of calcitonin gene‐related peptide (CGRP) (0.3 nmol). The concentration of CGRP in aqueous humour from untreated rabbit eyes was 0.1 +0.001 nmol 1−1. Irradiation of the iris raised the CGRP concentration to 8.9±1.5 nmol 1−1. L‐NAME (200 mg kg−1) greatly suppressed the irradiation‐evoked release of CGRP, the concentration in the aqueous humour being 1.2 ± 0.2 nmol 1−1 (P<0.001). L‐Arginine reversed the L‐NAME‐induced inhibition of release of CGRP, the concentration of CGRP in the aqueous humour being 9.7 ± 0.6 nmol 1−1. In addition, a NO donor, sodium nitroprusside (0.9 μmol), was found to raise the concentration of CGRP in the aqueous humour (14.8 ± 0.8 nmol 1−1) and to induce symptoms of ocular inflammation. The elevation in concentration of CGRP induced by sodium nitroprusside was not affected by L‐NAME (200 mg kg−1) (14.5 ± 1.2 nmol 1−1). Ocular responses were not inhibited by L‐NAME. 6 Our findings suggest that NO plays an important role in ocular inflammation by activating C‐fibres (directly or indirectly) and by mediating CGRP‐induced responses.

Immunological Studies of Chronic Ocular Toxoplasmosis: Up-Regulation of Major Histocompatibility Complex Class I and Transforming Growth Factor β and a Protective Role for Interleukin-6

“…The relative contribution of the host inflammatory response versus parasite proliferation in causing destruction of the retina has not been defined (29). The eye is an immuneprivileged site and inflammatory products such as tumor necrosis factor ␣ (TNF-␣), gamma interferon (IFN-␥), and nitric oxide production have been linked to experimental autoimmune uveitis (25,39). Under normal circumstances, the eye constitutively expresses transforming growth factor ␤ (TGF-␤) and has low levels of major histocompatibility complex (MHC) class I expression in order to down-regulate inflammatory mediators and the immune response (33).…”

Transgenic mice with ocular overexpression of an adrenomedullin receptor reflect human acute angle-closure glaucoma

“…However, physiological concentrations of approx. 10 −10 mol/l CGRP in the aqueous humour of mice only increased to 10 −8 mol/l in response to laser irradiation of the iris [36]. Taken together, CGRP predominantly facilitates trabecular outflow with a reduction in IOP, and AM, relaxing the pupillary sphincter muscle, dramatically increases IOP.…”

Direct, real-time, simultaneous monitoring of intravitreal nitric oxide and oxygen in endotoxin-induced uveitis in rabbits

“…EIU is widely accepted as an animal model of acute intraocular inflammation in humans (Rosenbaum et al, 1980;Howes et al, 1985;Kulkarni and Mancino, 1993;Jacquemin et al, 1996), which has been used in several studies to assess the role of NO generation in the resulting hyperemia, breakdown of the blood-aqueous barrier, and cellular infiltration (Parks et al, 1994;Wang and Hakanson, 1995;Mandai et al, 1996). Thus, NO has been implicated in the pathogenesis of EIU (Jacquemin et al, 1996;Parks et al, 1994;Bellot et al, 1994;Goureau et al, 1995).…”