advertisement
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)-1 could be involved in glaucomatous neuropathy. The purpose 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, whereas NOS-1, -2, and -3 levels were assessed by Western blotting. L-Arginine uptake was measured using 3H-l-arginine, whereas 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, -2, or -3 levels were observed in eyes injected with HA. L-Arginine influx and mRNA levels of cationic amino acid transporter type (CAT)-1 and -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.
Dr. N. Belforte, Laboratorio de Neuroquímica Retiniana y Oftalmología Experimental, Universidad de Buenos Aires, Centro de Estudios Farmacológicos y Botánicos, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)