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Involvement of AMPK in the retina of AMPK Knockout mice in experimental models of Diabetes and Proliferative Ischemic Retinopathy: in vivo and in vitro

Grant number: 18/07398-3
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2019
Effective date (End): July 31, 2021
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Jacqueline Mendonça Lopes de Faria
Grantee:Marcella Neves Dátilo
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Diabetes Mellitus (DM) is a disease characterized by Chronic Hyperglycemia and is associated with damage to several organs. Diabetic Retinopathy (DR) is a chronic complication of DM characterized by a premature and progressive neurological impairment that affects neural cells, glial cells, vascular elements and is considered one of the major causes of blindness in working age around the world. Despite the multiple hypotheses that propose mechanisms that explain how the Hyperglycemia starts the biochemical process involved in the pathogenesis of DR, the precise mechanism still unknown. Several studies showed that AMP-Activated Protein Kinase (AMPK) besides acting like an energetic sensor intracellular it is involved in other mechanisms of cellular homeostasis which makes it an important target of study. The involvement of AMPK in experimental models of DR remains unknown. Therefore, in this study, we will use 2 experimental models: 1. AMPK±1-/- and/or AMPK±2-/- diabetic or non-diabetic mice; 2. AMPK±1-/- and/or AMPK±2-/- mice submitted to hyperoxia (Retinopathy induced by oxygen). Thus, in the first experimental design we would evaluate the experimental Diabetic Retinopathy in its initial phases and in the second experimental design we would evaluate the late proliferative phase. To access the role of AMPK in Hyperglycemia conditions or hyperoxia, we aim to use rat retina Müller Cells of (rMC-1) and a Human Retinal Pigment Epithelial Cells (ARPE-19). The cells will be submitted to conditions of high glucose and/or hyperoxia in the presence or absence of a chemical activator/blocker of AMPK (AICAR and compound C, respectively) and will be also used a method for silencing the expression (small interfering RNA, siRNA) of AMPK. (AU)