Alterations in glutamate and nitric oxide metabolism in the RdS mice

Abstract

Aims/Purpose: Nitric oxide (NO) is an essential signalling molecule, with gaseous nature. NO is synthesized by the conversion of L‐arginine to L‐citrulline. This reaction is catalysed by the enzyme nitric oxide synthase (NOS). There are three NOS isoforms, but nNOS reflects most of the production of NO in the retina. Although NO is employed in the retina to maintain ocular function, it has also been related to different visual diseases. Increased levels of NO have been associated with ocular diseases involving increased glutamate concentrations, ischaemia, oxidative stress and inflammation (such as retinitis pigmentosa (RP)). The main purpose of this work was to determine glutamate retinal concentrations at different stages of the retinal degeneration that occurs in the rds mice and to study possible NO metabolism alterations.Methods: Rds mice were treated in accordance with the ARVO statement for the use of animals in ophthalmic and vision research. Mice were sacrificed at different postnatal days (11, 17, 21 and 28). Retinal glutamate concentrations were determined by high pressure liquid chromatography (HPLC). The expression of different enzymes related with NO metabolism (nNOS, guanylate cyclase (GC) and arginase) was determined by histochemistry.Results: Glutamate as well as nNOS was observed to be increased in the retina of rds mice mainly between the peak of rods and cones death. GC was observed to be decreased in the rds mice compared to control ones and no significant changes were observed in arginase expression when we compared rds and control mice.Conclusions: There are alterations in the expression of glutamate, nNOS and GC in rds mice retina compared to control mice. RP is a disease with no effective treatment to date and NO metabolism may be a new target in RP treatment.