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 Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2019
• End date: July 31, 2022
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Jacqueline Mendonça Lopes de Faria
• Grantee: Marcella Neves Dátilo
• Host 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)

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)

DATILO, MARCELLA N.; FORMIGARI, GUILHERME P.; LOPES DE FARIA, JOSE B.; LOPES DE FARIA, JACQUELINE M.. AMP kinase activation by Omega-3 polyunsaturated fatty acid protects the retina against ischemic insult: An in vitro and in vivo study. EXPERIMENTAL EYE RESEARCH, v. 226, p. 10-pg., 2022-12-18. (14/22687-0, 18/07398-3)

DATILO, M. N.; FORMIGARI, G. P.; LOPES DE FARIA, J. B.; LOPES DE FARIA, J. M.. The role of AMPK in the mechanism of ischaemic retinopathy: an in vitro study. Diabetologia, v. 63, n. SUPPL 1, p. 2-pg., 2020-09-01. (18/07398-3, 16/16655-4, 14/22687-0)

Academic Publications

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

DÁTILO, Marcella Neves. AMPK activation by omega-3 fatty acids protects the retina against ischemic insults. 2023. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.