Preserving vision in glaucoma: preventing optic neuropathy through neuroprotective, vasodilative treatment

Resumo

As millions of glaucoma patients lose sight, it is evident that there is a need to develop neuroprotective therapies that can be used to prevent retinal ganglion cell (RGC) death. Advances in understanding of the glaucoma make it evident that perfusion abnormalities are a key factor in the pathogenesis of glaucomatous neuropathy. Based on findings in similar diseases, we hypothesize that improving retinal and optic nerve blood flow can result in significant RGC protection in glaucoma. Sildenafil, a vasodilative drug that inhibits PDE5 has improved survival in several models of ischemic injury. We have preliminary results demonstrating that treatment of glaucomatous rats results in improved retinal function. In this proposal we aim to use a combination of molecular, structural and functional methods to test our hypothesis in the rat glaucoma model. Glaucoma will be induced, and rats will be treated with sildenafil, in Israel. Sequential electrophysiological recordings will be conducted to study the efficacy of treatment. Eyes of sacrificed animals will be shipped to Brazil for in vitro studies, including histological and IHC assessment of damage. Should our preliminary results be duplicated, positive results in such a comprehensive study may lead to a clinical trial of this safe and promising drug in glaucoma patients. (AU)