Deficiency in Retinal TGFβ Signaling Aggravates Neurodegeneration by Modulating Pro-Apoptotic and MAP Kinase Pathways
Bielmeier CB, Schmitt S, Kleefeldt N, Boneva SK, Schlecht A, Vallon M, Tamm ER, Hillenkamp J, Ergun S, Neueder A, Braunger BM (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 23
Article Number: 2626
Journal Issue: 5
DOI: 10.3390/ijms23052626
Abstract
Transforming growth factor β (TGFβ) signaling has manifold functions such as regulation of cell growth, differentiation, migration, and apoptosis. Moreover, there is increasing evidence that it also acts in a neuroprotective manner. We recently showed that TGFβ receptor type 2 (Tgfbr2) is upregulated in retinal neurons and Müller cells during retinal degeneration. In this study we investigated if this upregulation of TGFβ signaling would have functional consequences in protecting retinal neurons. To this end, we analyzed the impact of TGFβ signaling on photoreceptor viability using mice with cell type-specific deletion of Tgfbr2 in retinal neurons and Müller cells (Tgfbr2∆OC ) in combination with a genetic model of photoreceptor degeneration (VPP). We examined retinal morphology and the degree of photoreceptor degeneration, as well as alterations of the retinal transcriptome. In summary, retinal morphology was not altered due to TGFβ signaling deficiency. In contrast, VPP-induced photoreceptor degeneration was drastically exacerbated in double mutant mice (Tgfbr2∆OC; VPP) by induction of pro-apoptotic genes and dysregulation of the MAP kinase pathway. Therefore, TGFβ signaling in retinal neurons and Müller cells exhibits a neuroprotective effect and might pose promising therapeutic options to attenuate photoreceptor degeneration in humans.
Involved external institutions
Universitätsklinikum Würzburg
Germany (DE)
Albert-Ludwigs-Universität Freiburg
Germany (DE)
Julius-Maximilians-Universität Würzburg
Germany (DE)
Universität Regensburg
Germany (DE)
Universität Ulm
Germany (DE)
Germany (DE)
Albert-Ludwigs-Universität Freiburg
Germany (DE)
Julius-Maximilians-Universität Würzburg
Germany (DE)
Universität Regensburg
Germany (DE)
Universität Ulm
Germany (DE)
How to cite
APA:
Bielmeier, C.B., Schmitt, S., Kleefeldt, N., Boneva, S.K., Schlecht, A., Vallon, M.,... Braunger, B.M. (2022). Deficiency in Retinal TGFβ Signaling Aggravates Neurodegeneration by Modulating Pro-Apoptotic and MAP Kinase Pathways. International Journal of Molecular Sciences, 23(5). https://doi.org/10.3390/ijms23052626
MLA:
Bielmeier, Christina B., et al. "Deficiency in Retinal TGFβ Signaling Aggravates Neurodegeneration by Modulating Pro-Apoptotic and MAP Kinase Pathways." International Journal of Molecular Sciences 23.5 (2022).
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