Annexin A1 protein in retinogenesis and oxidative stress: Study in retinal organoids derived from human iPSCs

• Grant number: 24/04275-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Cristiane Damas Gil
• Grantee: Rafael André da Silva
• Supervisor: Maria Natalia Vergara
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: University of Colorado, Denver (CU), United States
• Associated to the scholarship: 22/12027-0 - ANNEXIN A1 PROTEIN IN DIABETIC RETINOPATHY INFLAMMATION, BP.DR

Abstract

Diseases that affect the retina have common triggers, such as oxidative stress, inflammation, and neuronal death in the retina. In the search for new potential therapeutic targets, retinal organoids emerge as a robust and technological platform that can aid in the discovery of new therapies. Annexin A1 (AnxA1) belongs to a family of proteins that bind to membrane phospholipids in a calcium-dependent manner. As a particular characteristic, AnxA1 is a protein with anti-inflammatory and pro-resolving activity, also participating in processes related to apoptosis and oxidative stress. In ocular diseases, the role of AnxA1 and the use of its mimetic peptide Ac2-26 as a pharmacological treatment have been investigated in different contexts such as uveitis, keratitis, glaucoma, and conjunctivitis, but little is known about its role in healthy retina and in conditions of damage. Studies conducted by our group in Brazil show that AnxA1 knockout animals present alterations in the retina's cone system and in ON-bipolar and OFF-bipolar cells. Additionally, in chronic diabetic retinopathy, AnxA1-/- animals show an exacerbated systemic inflammatory profile and increased retinal angiogenesis. Interestingly, the lack of AnxA1 in the retina is associated with negative regulation of gliosis. Thus, in the present project, we will evaluate the expression pattern of AnxA1 in in vitro retinogenesis, using retinal organoids derived from human induced pluripotent stem cells (iPSCs) at different stages of development. Furthermore, we will investigate the potential use of Ac2-26 in the response to oxidative stress in the retina in vitro using retinal organoids.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DA SILVA, RAFAEL ANDRE; DE LIMA, JOAO VITOR FERREIRA; DE MACEDO, RAQUEL FINK LINS E SILVA; SANT'ANA, MONIELLE; GIL, CRISTIANE DAMAS; VERGARA, M. NATALIA. Advances in immunomodulation for organ transplantation: The role of the Annexin A1/FPR axis. Clinics, v. 80, p. 2-pg., 2025-01-01. (21/00270-4, 24/04275-9)