Banca de QUALIFICAÇÃO: MARÍLIA INÊS MÓVIO

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE : MARÍLIA INÊS MÓVIO
DATA : 28/01/2025
HORA: 14:00
LOCAL: Sala 212 do Bloco Zeta do Campus de São Bernardo do Campo da Universidade Federal do ABC
TÍTULO:

Redirecting verteporfin as a potential therapeutic agent for retinitis pigmentosa: exploring neuroprotection and modulation of glial cell response

PÁGINAS: 120
RESUMO:

Retinitis pigmentosa (RP) is a leading cause of blindness, affecting more than 41 million people worldwide. The absence of a cure or widely accessible treatments often leads to hopelessness among patients. During the degenerative process, the primary cells affected are photoreceptors, specifically rods, and cones, initially due to gene mutations. In the autosomal recessive variation, the most common mutation is due to single-nucleotide polymorphism (SNP) in the PDE6B gene, which initiates a cascade of cell death, beginning with rods and subsequently triggering cone cell degeneration. Cone cell loss is associated with mechanisms such as oxidative stress, inflammatory responses, and excitotoxicity. Furthermore, the YAP/TEAD Hippo pathway appears to be implicated as a downstream effect of RP progression. One of the drugs that modulates YAP/TEAD Hippo pathway is the Verteporfin (VP), which acts on YAP phosphorylation and prevents the YAP/TEAD conjugation. VP is already approved for clinical use, mainly indicated as chemotherapy, and to treat other eye diseases that curse with neovascularization. Considering this information, and focusing on delaying secondary cell death and treating RP, we aim to investigate the drug redirecting Verteporfin (VP) as a potential treatment for RP. Therefore, we aimed i) to observe the possible relation with neuroprotection and neuroinflammatory rebalance in oxidative stress, inflammatory response, and excitotoxicity stimuli, ii) to observe the consequences of VP treatment in microglia and Müller cell modulation, and iii) to treat RP animal model with VP using the subretinal route aiming to delay cone cell death progression For in vivo experiments, VP was delivery at post-natal day 8 (P8), and the retinas were analyzed at P14 and P21. Our partial results indicate that VP exhibits significant neuroprotective effects, particularly under oxidative stress conditions, related to Müller and microglia modulation, as observed in conditioned medium experiments. In the RP animal model, VP treatment reduced cell death, improved retinal morphometry at P14 and P21, and preserved a greater number of rhodopsin-positive cells. These effects may correlate with alterations in glial cell activity after VP treatment. Taken together, our findings suggest that VP holds promise as a potential therapeutic agent for RP. However, further experiments are necessary to elucidate the role of glia-released factors in neuroprotection, potential shifts in microglial phenotype, and the precise mechanisms underlying VP’s effects.

MEMBROS DA BANCA:
Presidente - Interno ao Programa - 1994696 - SILVIA HONDA TAKADA
Membro Titular - Examinador(a) Interno ao Programa - 1675707 - FULVIO RIELI MENDES
Membro Titular - Examinador(a) Externo à Instituição - LUIZ ROBERTO GIORGETTI DE BRITTO
Membro Suplente - Examinador(a) Interno ao Programa - 1872537 - MARCELA BERMUDEZ ECHEVERRY