Banca de DEFESA: MARÍLIA INÊS MÓVIO
Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.DISCENTE : MARÍLIA INÊS MÓVIO
DATA : 08/10/2025
HORA: 14:00
LOCAL: Sala 211 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
PÁGINAS: 149
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 one of the autosomal recessive variations, the 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 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 the 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 that 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 of VP treatment with neuroprotection and neuroinflammatory rebalance in oxidative stress, inflammatory response and excitotoxicity stimuli; ii) to evaluate the VP treatment consequences in microglia and Müller cells modulation; and iii) by utilizing RP animal model with Pde6β mutation, to evaluate the possible consequences of VP treatment delivered by subretinal injection. In in vitro experiments, we used experimental protocols that mimetize cytotoxicity, oxidative stress and microglia activation in mixed and pure retinal primary cell cultures to evaluate, mechanistically, the role of VP. In vivo, VP drug was delivered in the eighth post-born day (P8), and the retina was analyzed in days P14 and P21. Our results indicate that VP exhibit significative neuroprotective effects, especially in oxidative stress conditions, related with Müller cells and microglia modulation, as observed in conditioned medium experiments. In the animal model of RP, VP treatment reduced cell death, mitigated the reduction of specific retinal layers at P14 and P21, and preserved photoreceptors. These effects could be related with modification in glial cell activity after VP treatment, whether related to the morphology, phenotype, or reactive gliosis of these cell types. Taken together, our findings suggest that VP has potential as a therapeutic agent for RP.
MEMBROS DA BANCA:
Presidente - Interno ao Programa - 1676367 - ALEXANDRE HIROAKI KIHARA
Membro Titular - Examinador(a) Interno ao Programa - 1872537 - MARCELA BERMUDEZ ECHEVERRY
Membro Titular - Examinador(a) Externo à Instituição - DANIELA MARIA OLIVEIRA BONCI - USP
Membro Titular - Examinador(a) Externo à Instituição - CAROLINA BELTRAME DEL DEBBIO - USP
Membro Titular - Examinador(a) Externo à Instituição - DANIEL MARTINS DE SOUZA
Membro Suplente - Examinador(a) Interno ao Programa - 1994696 - SILVIA HONDA TAKADA
Membro Suplente - Examinador(a) Interno ao Programa - 1675707 - FULVIO RIELI MENDES
Membro Suplente - Examinador(a) Externo à Instituição - LUCIANA SIMÕES RAFAGNIN MARINHO