@article{BielmeierSchmittKleefeldtetal.2022,
  author    = {Bielmeier, Christina B. and Schmitt, Sabrina I. and Kleefeldt, Nikolai and Boneva, Stefaniya K. and Schlecht, Anja and Vallon, Mario and Tamm, Ernst R. and Hillenkamp, Jost and Erg{\"u}n, S{\"u}leyman and Neueder, Andreas and Braunger, Barbara M.},
  title     = {Deficiency in retinal TGFβ signaling aggravates neurodegeneration by modulating pro-apoptotic and MAP kinase pathways},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {5},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23052626},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283971},
  year      = {2022},
  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 M{\"u}ller 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 M{\"u}ller cells (Tgfbr2\(_{ΔOC}\)) 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\(_{ΔOC}\); VPP) by induction of pro-apoptotic genes and dysregulation of the MAP kinase pathway. Therefore, TGFβ signaling in retinal neurons and M{\"u}ller cells exhibits a neuroprotective effect and might pose promising therapeutic options to attenuate photoreceptor degeneration in humans.},
  language  = {en}
}