Single-cell RNA sequencing analysis of sickle cell retinopathy in retinas of humanized HbSS-Townes mice

• Grant number: 23/15233-2
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): October 01, 2024
• Effective date (End): July 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Mônica Barbosa de Melo
• Grantee: Ana Carolina Lima Camargo
• Supervisor: Rui Chen
• Host Institution: Centro de Biologia Molecular e Engenharia Genética (CBMEG). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Research place: University of California, Irvine (UC Irvine), United States
• Associated to the scholarship: 21/10159-3 - Identification of proteins involved in Sickle Cell Retinopathy in retinas of humanized mice HbSS-Townes, BP.PD

Abstract

Proliferative sickle cell retinopathy (PSCR) is the most severe ophthalmological disorder in patients with sickle cell anemia (SCA). The pathophysiology of the disorder includes sickle cell aggregation, endothelial activation, and thromboinflammatory cascades, leading to artery occlusion in the peripheral retina. The resulting ischemia stimulates neovascularization with fragile vessels. This can lead to vitreous hemorrhage and retinal detachment, causing vision loss. Due to the complex pathophysiology and clinical relevance of PSCR, it is important to understand the molecular mechanisms involved in this disorder. The retina is a complex tissue with several cell types. Single-cell RNA sequencing is a robust method for characterizing different cell types in complex tissues and exploring gene expression at the single-cell level. Considering the difficulties in extracting human retinal tissue and the altered mechanisms in the retina of patients with SCA, this study aims to evaluate and characterize the single-cell transcriptome from the retina of humanized HbSS and HbAA Townes mice. Identifying gene expression at the single-cell level and carrying out functional enrichment analyses of the retina with PSCR will enable the identification of crucial (or rare) genes involved in the pathogenesis of PSCR and, consequently, potential biomarkers and therapeutic targets.