The role of AMPK in the neural-retina and blood-retinal barrier in a model of experimental diabetes in mice knockout for AMPKalpha-1 and AMPKalpha-2. New perspective in the pharmacological treatment of diabetic retinopathy

• Grant number: 15/23258-9
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): March 01, 2016
• Effective date (End): February 28, 2019
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Jose Butori Lopes de Faria
• Grantee: Diego Andreazzi Duarte
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 14/22687-0 - Contribution of AMPK pathway to renal fibrosis and pathogenesis of diabetic nephropathy and retinopathy, AP.TEM

Abstract

Diabetic retinopathy (DR) is the principal cause of blindness in people worldwide adulthood. This complication presents neurodegenerative initial aspects followed by deep vascular changes. The treatments depend on invasive methods, which often are not enough in delaying disease progression. Therefore, a better understanding of the initial phenomena of DR can helpful to identify new therapeutic targets and prevent the advanced and irreversible changes of the disease. The AMP-activated protein kinase (AMPK) is a family of proteins that maintains the balance between production and consumption of ATP in eukaryotic cells and is related to the pathogenesis of several chronic diseases such as cancer, heart disease and diabetes. The aim of this project will be evaluate the role of AMPK in retina in a model of experimentally diabetic and in retinal cells, both, manipulated genetically or not to deletion of catalytic subunit of the AMPK. Therefore, will be used a mouse model of experimentally diabetic genetically modified or not to deletion of the alpha-1 and alpha-2 subunits of AMPK. As vitro model, rat retinal Müller cells (rMC-1) and mouse retinal pigmented epithelial cells (ARPE-19) will be manipulated generically and/or pharmacologically to deletion or activation of the AMPK. In both, in vivo and in vitro models, will be accessed markers of diabetic retinopathy, inflammation and oxidative stress; in addition will be measured the retinal activity in mice by electroretinogram and evaluated in ARPE-19 cell culture the permeability and cellular resistance.

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)

LOPES DE FARIA, JACQUELINE M.; DUARTE, DIEGO A.; SIMO, RAFAEL; GARCIA-RAMIREZ, MARTA; DATILO, MARCELLA N.; PASQUALETTO, FRANCIELI C.; LOPES DE FARIA, JOSE B.. delta Opioid Receptor Agonism Preserves the Retinal Pigmented Epithelial Cell Tight Junctions and Ameliorates the Retinopathy in Experimental Diabetes. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, v. 60, n. 12, p. 3842-3853, SEP 2019. (15/23258-9)