Retinal characterization in Townes mice model: Morphological parameters and gene expression of inflammatory and angiogenic markers

• Grant number: 25/01351-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Mônica Barbosa de Melo
• Grantee: Julia Dezordi Acacio
• 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 concerning ocular morbidity in sickle cell diseases. This complication occurs due to vaso-occlusion of the ocular microvasculature, resulting from endothelial activation, inflammatory cascades, adhesion, and coagulation. Consequently, neovascularization may occur, potentially leading to vitreous hemorrhage and retinal detachment, which are the primary causes of progressive vision loss in affected patients. The precise cause of new blood vessels formation in sickle cell diseases is not yet fully understood, thus, retinopathy in these patients is an interesting study model.Due to the inherent challenges of assessing human retinal tissue, the HbSS-Townes mouse model is the most suitable, as these animals exhibit a phenotype similar to human retinopathy. This project proposes the morphological characterization of the retina in Townes mice and C57BL/6J controls using hematoxylin and eosin staining, as well as the evaluation of gene expression by RT-qPCR of inflammatory markers: Interleukin 6 (IL-6), Interleukin 1¿ (IL-1¿), and Tumor Necrosis Factor ¿ (TNF-¿), along with angiogenesis markers: Vascular Endothelial Growth Factor (VEGF) and Hypoxia-Inducible 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, particularly in its proliferative form.