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Expression of PDE6B in a neurodegenerative model of retinitis pigmentosa in vitro for inhibition of necroptosis

Grant number: 21/14227-3
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): May 01, 2022
Effective date (End): April 30, 2024
Field of knowledge:Biological Sciences - Genetics - Animal Genetics
Principal Investigator:Alexandre Hiroaki Kihara
Grantee:Gabrieli Bovi dos Santos
Host Institution: Centro de Matemática, Computação e Cognição (CMCC). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil


The retina can be affected by several types of diseases, with or without origin in genetic alterations, that can compromise both its morphological structure and the survival of specific cells. Among these diseases is retinitis pigmentosa (RP), an hereditary disease with several related mutations, especially in genes that encode proteins required for phototransduction in rods. RP with mutations in the phosphodiesterase 6 B (PDE6B) gene, leads to the lost of rods by the elevated toxic level of cyclic guanosine monophosphate (cGMP). Mutation in PDE6² alters cell activity that results in apoptosis, but recently a new cell death pathway has been linked to RP, necroptosis. Necroptosis can be considered as a 'programmed necrosis' and furthermore can influence the transcription of inflammatory genes, and the literature on necroptosis in RP is scarce. The aim of this work is to establish an in vitro RP model in pure photoreceptor cell cultures submitted to light and to observe the relationship of necroptosis with the PDE6² gene. By doing so, we aim to establish an in vitro model that can recapitulate the loss of photoreceptors that happens during the progression of RP. Obtaining this model may be useful for testing new molecules and gene manipulations aiming to establish therapeutic strategies for the treatment of RP.

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