Effect of ocular hypertension on the retinal nitridergic pathway

BELFORTE, NICOLAS; MORENO, MARIA; CYMERYNG, CORA; BORDONE, MELINA; KELLER SARMIENTO, MARIA; ROSENSTEIN, RUTH

Buenos Aires,

Congreso; XVII International Congress of Eye Research; 2006

International Society of Eye Research

Several lines of evidence support the involvement of nitric oxide (NO) on glaucomatous neuropathy. However, controversial results on the retinal nitridergic activity were reported in different models of experimental glaucoma. In this context, the aim of this work was to examine the retinal nitridergic pathway activity in eyes with ocular hypertension induced by hyaluronic acid (HA). For this purpose, weekly injections of HA were performed unilaterally in the rat anterior chamber, whereas the contralateral eye was injected with saline solution. At 3 or 6 weeks of treatment, NOS activity was assessed through the conversion of 3H-L-arginine to 3H-citrulline, while retinal NOS-2 levels were measured by Western blot. L-arginine uptake was measured in a retinal synaptosomal fraction using 3H-arginine. In addition, cyclic guanosine monophosphate (cGMP) levels were assessed by radioimmunoassay, while mRNA levels of arginine transporters were evaluated through semiquantitative RT-PCR. At 3 or 6 weeks of treatment, retinal NOS activity significantly increased in eyes injected with HA, whereas no differences in NOS-2 levels were observed. L-arginine influx as well as mRNA levels of cationic aminoacid transporters (CAT-1 and CAT-2) significantly increased in HA treated eyes for 3 or 6 weeks. After 3 but not 6 weeks of treatment, accumulation of cGMP was significantly higher in HA- than in vehicle- injected eyes. These results indicate a significant overactivation of the retinal nitridergic pathway in hypertensive eyes, supporting the involvement of NO in glaucomatous neuropathy.