Utilizing flavonoids for the treatment of autosomal recessive retinitis pigmentosa: a nutraceutical approach

• Grant number: 24/00828-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: October 01, 2024
• End date: September 30, 2028
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Alexandre Hiroaki Kihara
• Grantee: Théo Henrique de Lima Vasconcellos
• Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

The retina is a photosensitive neuroepithelium found in the inner region of the eye and is considered an integral component of the central nervous system (CNS). An imbalance in the physiological conditions or changes in the number of functional photoreceptors can lead to significant visual deficits. One such disease that virtually leads to vision impairment is retinitis pigmentosa (RP). Among the causes of autosomal recessive RP (arRP) are mutations in the PDE6B gene, culminating in the initial cell death of rod-type photoreceptors and subsequent degradation of cones. However, the processes underlying the primary cell death of rods are not fully known, although studies point to mechanisms involved in the inflammatory response, oxidative and metabolic stress, epigenetic factors, and calcium dysregulation. Nutraceutical therapies, incorporating bioactive compounds like flavonoids, show promise in addressing neurodegenerative conditions. Rutin, sourced from plants like buckwheat and cherries, exhibits multifaceted benefits, including antioxidant, anti-inflammatory, antidiabetic, and antitumoral effects. Notably, rutin interacts with critical signaling pathways associated with RP physiopathology, such as NF-kB, JAK/STAT, Akt/PTEN, and MAPK. Given this information, this project aims to investigate rutin's potential as a therapeutic candidate for autosomal recessive RP. Utilizing in vitro approaches with primary retinal cell cultures, retinal organoids in collaboration with experts at the University of Southern California, the research will explore various treatment strategies, including acute local injection, chronic systemic treatment, and nutraceutical therapy. The utilization of animal models RD1 and RD10 adds depth to the investigation, aiming to improve the understanding of rutin efficacy in mitigating neurodegenerative processes in the retina. In summary, the project seeks to develop new therapies of arRP, offering a multidimensional approach that integrates in vitro and animal models to address the complex challenges posed by RP's diverse genetic mutations and cellular events. (AU)