Ex Vivo Model of Spontaneous Neuroretinal Degeneration for Evaluating Stem Cells’ Paracrine Properties

Fernandez-Bueno, Iván

doi:10.1007/978-1-0716-1225-5_9

Cited by 2 publications

(4 citation statements)

References 42 publications

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“…The retinal spontaneous degeneration model used for this study is an excellent alternative to study the molecular and cellular changes that occur during retinal degenerative diseases since they retain the complex neuroretinal architecture, interactions of neuroretinal cells, and mimic the in situ responses under controlled conditions (Li et al, 2018;Murali et al, 2019;Fernandez-Bueno and Usategui-Martin, 2021). However, it presents the drawback of lacking both retinal and choroidal vascularization, the axotomy of retinal ganglion cells, and the absence of retinal pigmented epithelium, for that reason, this can only resemble the degeneration of the neuroretina, a joint event in most retinal neurodegenerative diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Organ neuroretinal explants cultures were used as a spontaneous neuroretinal degeneration model described by Fernandez-Bueno and Usategui- Martin (2021). As a summary, we used fresh eyes extracted from pigs 6 to 8 months derived from the local slaughterhouse.…”

Section: In Vitro Model Of Spontaneous Neuroretinal Degenerationmentioning

confidence: 99%

“…In vitro retinal explant cultures are helpful tools for studying neuroretinal degeneration processes because they replicate, with in vitro limitations, the cellular and molecular changes that occur in retina degeneration (Li et al, 2018;Murali et al, 2019;Fernandez-Bueno and Usategui-Martin, 2021). Although this model does not mimic a specific retinal disease, it resembles neurodegeneration, a joint event in most RND (Cuenca et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Programmed Cell Death and Autophagy in an in vitro Model of Spontaneous Neuroretinal Degeneration

et al. 2022

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Retinal neurodegenerative diseases are the leading causes of visual impairment and irreversible blindness worldwide. Although the retinal response to injury remains closely similar between different retinal neurodegenerative diseases, available therapeutic alternatives are only palliative, too expensive, or very specific, such as gene therapy. In that sense, the development of broad-spectrum neuroprotective therapies seems to be an excellent option. In this regard, it is essential to identify molecular targets involved in retinal degeneration, such as cell death mechanisms. Apoptosis has been considered as the primary cell death mechanism during retinal degeneration; however, recent studies have demonstrated that the only use of anti-apoptotic drugs is not enough to confer good neuroprotection in terms of cell viability and preservation. For that reason, the interrelationship that exists between apoptosis and other cell death mechanisms needs to be characterized deeply to design future therapeutic options that simultaneously block the main cell death pathways. In that sense, the study aimed to characterize the programmed cell death (in terms of apoptosis and necroptosis) and autophagy response and modulation in retinal neurodegenerative diseases, using an in vitro model of spontaneous retinal neurodegeneration. For that purpose, we measured the mRNA relative expression through qPCR of a selected pool of genes involved 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 showed an increase of pro-apoptotic and pro-necroptotic related genes and proteins during in vitro retinal neurodegeneration. Besides, we describe for the first time the modulation between programmed cell death mechanisms and autophagy in an in vitro retinal neurodegeneration model. This study reinforces the idea that cell death mechanisms are closely interconnected and provides new information about molecular signaling and autophagy along the retinal degeneration process.

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Section: Discussionmentioning

confidence: 99%

Section: In Vitro Model Of Spontaneous Neuroretinal Degenerationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Programmed Cell Death and Autophagy in an in vitro Model of Spontaneous Neuroretinal Degeneration

et al. 2022

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“…The NR explants were obtained less than 2 hours after enucleation, as described. 16 Four adjacent NR explants from the area centralis (i.e., the cone-enriched visual streak without blood vessels) were obtained from each eye (n = 32). The explants were laid on Transwell membranes 24 mm in diameter with a 0.4-mm-pore polycarbonate membrane insert (Corning Life Sciences) with the photoreceptor layer facing the membrane.…”

Section: Methodsmentioning

confidence: 99%

Retinal Neuroprotective Effect of Mesenchymal Stem Cells Secretome Through Modulation of Oxidative Stress, Autophagy, and Programmed Cell Death

Puertas‐Neyra

Galindo-Cabello

Hernández-Rodríguez

et al. 2022

Invest. Ophthalmol. Vis. Sci.

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Purpose Degenerative mechanisms of retinal neurodegenerative diseases (RND) share common cellular and molecular signalization pathways. Curative treatment does not exist and cell-based therapy, through the paracrine properties of mesenchymal stem cells (MSC), is a potential unspecific treatment for RND. This study aimed to evaluate the neuroprotective capability of human bone marrow (bm) MSC secretome and its potential to modulate retinal responses to neurodegeneration. Methods An in vitro model of spontaneous retinal neurodegeneration was used to compare three days of monocultured neuroretina (NR), NR cocultured with bmMSC, and NR cultured with bmMSC secretome. We evaluated retinal morphology markers (Lectin peanut agglutinin, rhodopsin, protein kinase C α isoform, neuronal-specific nuclear protein, glial fibrillary acidic protein, TdT-mediated dUTP nick-end labeling, and vimentin) and proteins involved in apoptosis (apoptosis-inductor factor, caspase-3), necroptosis (MLKL), and autophagy (p62). Besides, we analyzed the relative mRNA expression through qPCR of genes involved in apoptosis ( BAX, BCL2, CASP3, CASP8, CASP9 ), necroptosis ( MLKL, RIPK1, RIPK3 ), autophagy ( ATG7 , BCLIN1, LC3B , mTOR , SQSTM1 ), oxidative stress ( COX2, CYBA, CYBB, GPX6, SOD1, TXN2, TXNRD1 ) and inflammation ( IL1, IL6, IL10, TGFb1, TNFa ). Results The bmMSC secretome preserves retinal morphology, limits pro-apoptotic– and pro-necroptotic–related gene and protein expression, modulates autophagy-related genes and proteins, and stimulates the activation of antioxidant-associated genes. Conclusions The neuroprotective ability of the bmMSC secretome is associated with activation of antioxidant machinery, modulation of autophagy, and inhibition of apoptosis and necroptosis during retinal degeneration. The neuroprotective effect of bmMSC secretomes in the presence/absence of MSC looks similar. Our current results reinforce the hypothesis that the human bmMSC secretome slows retinal neurodegeneration and may be a therapeutic option for treating RND.

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Ex Vivo Model of Spontaneous Neuroretinal Degeneration for Evaluating Stem Cells’ Paracrine Properties

Cited by 2 publications

References 42 publications

Programmed Cell Death and Autophagy in an in vitro Model of Spontaneous Neuroretinal Degeneration

Programmed Cell Death and Autophagy in an in vitro Model of Spontaneous Neuroretinal Degeneration

Retinal Neuroprotective Effect of Mesenchymal Stem Cells Secretome Through Modulation of Oxidative Stress, Autophagy, and Programmed Cell Death

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