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The role of PAF receptor in retinal stem cell reprogramming and differentiation

Grant number: 20/11352-9
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): April 01, 2021
Effective date (End): July 31, 2023
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Carolina Beltrame Del Debbio
Grantee:Bárbara Dalmaso
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:15/24001-1 - MicroRNAs role in retinal stem cells regulation, AP.JP

Abstract

According to the International Council of Ophthalmology, degenerative retinal diseases are a worldwide public health problem, being one of the main causes of visual loss in humans. Currently, the cure for these diseases is not available in clinics, and therapies involving the use of stem cells are being considered promising therapeutic approaches. In this context, quiescent stem cells have been identified in the mammalian Ciliary Epithelium (EC), a tissue located between the retina and iris. Despite the clinical advantages, stem cells derived from EC do not completely extinguish the expression of parental genes, maintaining epithelial and pigmentation characteristics, which compromises their regenerative potential. Thus, for the development of future therapeutic approaches, it is essential to understand the mechanisms that regulate the physiology of EC in retinal stem cells. Experimental studies indicate that the lipid PAF (Platelet Activating Factor), through its receptor (PAFR) influences the proliferation, apoptosis, and differentiation of different cell types, including retinal progenitors. In addition, it is known that PAFR is directly involved with the regulation of important mediators of cell reprogramming, neurogenesis, and synaptogenesis. Based on this premise, the main objective of this work is to evaluate the effect of PAFR activation on retinal stem cells, with the purpose of understanding its influence on the maintenance of the progenitor phenotype during the processes of cell stemness, differentiation, and retinogenesis.