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

• Grant number: 11/51269-4
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2012
• End date: May 31, 2014
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
• Agreement: Hebrew University of Jerusalem - HUJ
• Principal Investigator: José Luiz Laus
• Grantee: José Luiz Laus
• Principal researcher abroad: Ron Ofri
• Institution abroad: Hebrew University of Jerusalem, Israel
• Host Institution: Faculdade de Ciências Agrárias e Veterinárias (FCAV). Universidade Estadual Paulista (UNESP). Campus de Jaboticabal. Jaboticabal , SP, Brazil

Abstract

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

ZANONI, DIOGO S.; DA SILVA, GERMANA A.; EZRA-ELIA, RAAYA; CARVALHO, MARCIO; QUITZAN, JULIANY G.; OFRI, RON; LAUS, JOSE L.; LAUFER-AMORIM, RENEE. Histological, morphometric, protein and gene expression analyses of rat retinas with ischaemia-reperfusion injury model treated with sildenafil citrate. International Journal of Experimental Pathology, v. 98, n. 3, p. 147-157, JUN 2017. (11/51269-4, 13/01926-4)

EZRA-ELIA, RAAYA; DA SILVA, GERMANA ALEGRO; ZANONI, DIOGO SOUSA; LAUFER-AMORIM, RENEE; COUTO DO AMARAL, ANDREIA VITOR; LAUS, JOSE LUIZ; OFRI, RON. Functional and Structural Evaluation of Sildenafil in a Rat Model of Acute Retinal Ischemia/Reperfusion Injury. CURRENT EYE RESEARCH, v. 42, n. 3, p. 452-461, 2017. (11/51269-4)