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Development of retinal organoids derived from patients with retinal degeneration to study regeneration mechanisms and therapeutic strategies

Grant number: 22/02105-3
Support Opportunities:Scholarships abroad - Research
Effective date (Start): August 01, 2022
Effective date (End): July 31, 2023
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Carolina Beltrame Del Debbio
Grantee:Carolina Beltrame Del Debbio
Host Investigator: Anand Swaroop
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: National Institutes of Health, Bethesda (NIH), United States  


According to the International Council of Ophthalmology, retinal degenerative diseases are a worldwide public health problem, being one of the main causes of human visual loss. Therapies involving the use of stem cells are being considered promising therapeutic approaches. The experimental models used to study retinal development and visual system pathologies have some limitations, as many clinical aspects are not observed in existing animal models. Today, the technology to create a retina in the lab is a reality: organoid culture. This complex model allows the testing of different treatments, drugs, biomolecules and viral vectors in a model that mimics the patient's pathological condition. In addition, the model does not run into ethical dilemmas of experimentation and has a renewable source of cells, without harm to the donor. This project aims to establish a personalized organoid culture model of the retina from somatic cells collected from patients with Age-Related Macular Degeneration (AMD), a retinopathy that affects close to 30 percent of the population between 52 and 60 years old. From the organoid retina derived from these patients, we will study the regeneration mechanisms present during the development of the disease, as well as the possible cellular, molecular and genetic alterations that occur during the degenerative process. We will also evaluate the expression of microRNAs and the PAF (platelet activating factor) pathway, known agents of retinal differentiation, during in vitro retinal formation. The results of this proposal will allow a better understanding of the regenerative and degenerative mechanisms involved in AMD, the establishment of a specialized experimental model and the possible elaboration of alternative therapeutic approaches. (AU)

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