Gene and protein expression of apoptosis pathways in Glaucoma induced in rat

• Grant number: 13/01926-4
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2013
• End date: April 30, 2015
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Renee Laufer Amorim
• Grantee: Diogo Sousa Zanoni
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

As millions of glaucoma patients lose sight, it has become accepted that there is a need to develop neuroprotective therapies that can be used, in conjunction with hypotensive drugs, to prevent retinal ganglion cell (RGC) death. Recent advances in the understanding of the pathophysiology of glaucoma make it evident that local ischemia and 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 and prevent vision loss in glaucoma. Sildenafil, a vasodilative drug that inhibits PDE5, thereby increasing cGMP levels and prolonging NO effects, has been shown to improve survival in several models of ischemic injury. This is a project that is part of Fapesp project with Jerusalem University (2011/51269-4 - RESERVING VISION IN GLAUCOMA.PREVENTING OPTIC NEUROPATHY THROUGH NEUROPROTECTIVE, VASODILATIVE TREATMENT (FAPESP-HUJ, PI: Dr Ron Ofri and Dr Jose Luiz Laus).Part of the study will be done in Israel, by Dr Ron Ofri, part in FCAV, by Dr Jose Luiz Laus, Unesp, Jaboticabal and part in FMVZ, Unesp, Botucatu. In this proposal we aim to use a combination of molecular, structural and functional methods to test our hypothesis in two different rat glaucoma models. Glaucoma will be induced, and rats will be treated with sildenafil, in Israel. Sequential electrophysiological recordings will be conducted to monitor progression of disease and efficacy of treatment. Eyes of sacrificed animals will be shipped to Brazil for in vitro studies, including qRT-PCR, 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.

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)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

ZANONI, Diogo Sousa. Experimental glaucoma model (ischemia and reperfusion): histology, morphometry, protein and gene espression of apoptosis pathway. 2015. Master's Dissertation - Universidade Estadual Paulista (Unesp). Faculdade de Medicina Veterinária e Zootecnia. Botucatu Botucatu.