Mineralocorticoid receptor pathway in glaucoma neuropathy

• Grant number: 25/05281-5
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2029
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Maria Fernanda Abalem de Sá Carricondo
• Grantee: Maria Fernanda Abalem de Sá Carricondo
• Principal researcher abroad: Francine Behar-Cohen
• Institution abroad: Université Paris-Sorbonne (Paris 4) , France
• Host Institution: Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• City of the host institution: São Paulo
• Associated researchers: Augusto Paranhos Junior ; MARCELO HATANAKA ; Maria Candida Barisson Villares Fragoso ; Mariana Botrel Cunha ; Pedro Carlos Carricondo ; Tiago dos Santos Prata

Abstract

Glaucoma is one of the leading causes of irreversible blindness worldwide, affecting millions and placing a significant burden on healthcare systems. Despite advances in intraocular pressure (IOP) control, glaucomatous neuropathy (GN) can progress even at normal IOP levels, particularly in normal-tension glaucoma (NTG). Emerging evidence indicates that oxidative stress, neuroinflammation, and hormonal dysregulation play key roles in retinal ganglion cell (RGC) degeneration. This project will investigate the role of the mineralocorticoid receptor (MR) pathway in GN pathogenesis, including its activation by endogenous glucocorticoids independently of aldosterone. Using transgenic animal models, human samples, and advanced techniques such as steroidomics and immunohistochemistry, we aim to identify MR-regulated molecular biomarkers and validate their involvement in GN. Additionally, we will assess the neuroprotective effects of spironolactone, an MR antagonist, in preclinical models and evaluate a novel ocular formulation for sustained release. This project is a collaborative effort between teams in Brazil and France, with a strong translational focus. It aims to provide the foundation for a future clinical trial using spironolactone eye drops. The findings are expected to have a direct clinical impact by offering alternative therapies for patients with glaucoma resistant to IOP reduction. (AU)