PROTEOMIC ANALYSIS IN SICKLE CELL RETINOPATHY IN RETINAS OF HUMANIZED HBSS-TOWNES MICE

• Grant number: 24/03283-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: December 01, 2024
• End date: January 31, 2028
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Mônica Barbosa de Melo
• Grantee: Júlia Nicoliello Pereira de Castro
• Host Institution: Centro de Biologia Molecular e Engenharia Genética (CBMEG). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 19/18886-1 - Pathophysiological mechanisms and treatment of red blood cell abnormalities, AP.TEM

Abstract

Proliferative sickle cell retinopathy (PSCR) is the ophthalmological alteration with the most relevance regarding ocular morbidity in the group of sickle cell diseases. The pathophysiology involves the aggregation of sickle red blood cells, activation of the endothelium, and thromboinflammatory cascades, leading to arteriolar occlusion of the peripheral retina. In proliferative SCR, the resulting ischemia stimulates neovascularization with the formation of fragile vessels, which can lead to vitreous hemorrhage and retinal detachment, resulting in vision loss. The complex pathophysiology and clinical significance reaffirm the importance of a better understanding of the molecular mechanisms involved in SCR. Due to the intrinsic difficulties in assessing human retinal tissue, the present project proposes the evaluation, characterization, and proteomic analysis of humanized HbSS-Townes and HbAA C57BL/6J mice retinas. Proteomic analysis by liquid chromatography-tandem mass spectrometry is robust and sensitive, capable of evaluating and comparing the global protein profile of the retina. The identification of differentially expressed proteins (DEPs) in SCR, followed by functional enrichment analysis and validation of the expression profile of the main proteins obtained will enable the identification of relevant proteins to the pathogenesis of SCR, and consequently, potential biomarkers and therapeutic targets.