RT info:eu-repo/semantics/article
T1 Programmed Cell Death and Autophagy in an in vitro Model of Spontaneous Neuroretinal Degeneration
A1 Puertas Neyra, Kevin Louis
A1 Galindo Cabello, Nadia Regina
A1 Hernández Rodríguez, Leticia Adriana
A1 González Pérez, Fernando
A1 Rodríguez Cabello, José Carlos
A1 González Sarmiento, Rogelio
A1 Pastor Jimeno, José Carlos
A1 Usategui Martín, Ricardo
A1 Fernández Bueno, Iván
AB Retinal neurodegenerative diseases are the leading causes of visual impairment andirreversible blindness worldwide. Although the retinal response to injury remains closelysimilar between different retinal neurodegenerative diseases, available therapeuticalternatives are only palliative, too expensive, or very specific, such as gene therapy.In that sense, the development of broad-spectrum neuroprotective therapies seemsto be an excellent option. In this regard, it is essential to identify molecular targetsinvolved in retinal degeneration, such as cell death mechanisms. Apoptosis has beenconsidered as the primary cell death mechanism during retinal degeneration; however,recent studies have demonstrated that the only use of anti-apoptotic drugs is notenough to confer good neuroprotection in terms of cell viability and preservation. Forthat reason, the interrelationship that exists between apoptosis and other cell deathmechanisms needs to be characterized deeply to design future therapeutic options thatsimultaneously block the main cell death pathways. In that sense, the study aimedto characterize the programmed cell death (in terms of apoptosis and necroptosis)and autophagy response and modulation in retinal neurodegenerative diseases, usingan in vitro model of spontaneous retinal neurodegeneration. For that purpose, wemeasured the mRNA relative expression through qPCR of a selected pool of genesinvolved in apoptosis (BAX, BCL2, CASP3, CASP8, and CASP9), necroptosis (MLKL,RIPK1, and RIPK3), and autophagy (ATG7, BCLIN1, LC3B, mTOR, and SQSTM1);besides, the immunoexpression of their encoding proteins (Casp3, MLKL, RIPK1,LC3B, and p62) were analyzed using immunohistochemistry. Our results showedan increase of pro-apoptotic and pro-necroptotic related genes and proteins duringin vitro retinal neurodegeneration. Besides, we describe for the first time the modulation between programmed cell death mechanisms and autophagy in an in vitro retinalneurodegeneration model. This study reinforces the idea that cell death mechanismsare closely interconnected and provides new information about molecular signaling andautophagy along the retinal degeneration process.
YR 2022
FD 2022
LK https://uvadoc.uva.es/handle/10324/71462
UL https://uvadoc.uva.es/handle/10324/71462
LA eng
NO Frontiers in Neuroanatomy 2022;16:812487
NO Producción Científica
DS UVaDOC
RD 28-dic-2024