Characterization of the retina in a Townes mouse model: Morphological parameters and evaluation of protein targets.

• Grant number: 25/26239-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2025
• End date: November 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Mônica Barbosa de Melo
• Grantee: Mariana de Sousa Pereira de Oliveira
• 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

Sickle cell retinopathy (SCR) is the most significant ophthalmological complication in relation to ocular morbidity in sickle cell disease. This complication occurs due to vaso-occlusion of the ocular microvasculature, resulting from endothelial activation, inflammatory cascades, and adhesion and coagulation. Consequently, neovascularization can occur, eventually leading to vitreous hemorrhage and retinal detachment, being the leading cause of progressive vision loss in affected individuals. The precise cause of neovascularization in sickle cell disease is not fully understood, making retinopathy in these individuals an interesting model for study. Due to the inherent difficulties in evaluating human retinal tissue, the HbSS-Townes mouse model is the most appropriate, as these animals exhibit a phenotype similar to human retinopathy. This project proposes the morphological characterization of the retina of Townes HbSS and Townes HbAA mice (controls) by hematoxylin and eosin staining, as well as the identification, by immunohistochemistry, of the NR5A2 target (Nuclear Receptor Subfamily 5 Group A Member 2) and angiogenesis markers: Vascular Endothelial Growth Factor (VEGF) and Hypoxia-Induced Factor 1 and 2 (HIF-1 and HIF-2). The characterization of morphological and molecular alterations will contribute to a better understanding of the pathophysiology of sickle cell retinopathy, especially in its proliferative form. (AU)