Abstract
Purpose::
Understanding the mechanisms of neuronal cell death in glaucoma is important for devising new treatments. Excitatory amino acids, excessive Ca2+ influx, and formation of nitric oxide (NO) via NO synthase (NOS) could be involved in glaucomatous neuropathy. The aim of the present study was to examine the retinal nitridergic pathway activity in rats exposed to experimentally elevated intraocular pressure.
Methods::
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, retinal NOS activity was assessed through the conversion of 3H-L-arginine to 3H-L-citrulline, while NOS-1, NOS-2, and NOS-3 levels were assessed by Western blotting. L-arginine uptake was measured using 3H-L-arginine, while mRNA levels of L-arginine transporters were determined by semiquantitative RT-PCR. In addition, cyclic guanosine monophosphate (cGMP) levels were quantified by radioimmunoassay
Results::
At both 3 and 6 weeks of treatment, NOS activity significantly increased in HA-injected eyes although no changes in retinal NOS-1, NOS-2, or NOS-3 levels were observed in eyes injected with HA. L-arginine influx and mRNA levels of cationic aminoacid transporter type 1 and 2 (CAT-1 and CAT-2) significantly increased in retinas from hypertensive eyes. Retinal cGMP levels significantly increased in eyes injected with HA for 3 but not 6 weeks.
Conclusions::
These results suggest a significant activation of the retinal nitridergic pathway in hypertensive eyes.
Keywords: nitric oxide • retina: neurochemistry • pathology: experimental