TY  - JOUR
A1  - Bielmeier, Christina B.
A1  - Schmitt, Sabrina I.
A1  - Kleefeldt, Nikolai
A1  - Boneva, Stefaniya K.
A1  - Schlecht, Anja
A1  - Vallon, Mario
A1  - Tamm, Ernst R.
A1  - Hillenkamp, Jost
A1  - Ergün, Süleyman
A1  - Neueder, Andreas
A1  - Braunger, Barbara M.
T1  - Deficiency in retinal TGFβ signaling aggravates neurodegeneration by modulating pro-apoptotic and MAP kinase pathways
JF  - International Journal of Molecular Sciences
N2  - 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\(_{ΔOC}\)) 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 Müller cells exhibits a neuroprotective effect and might pose promising therapeutic options to attenuate photoreceptor degeneration in humans.
KW  - TGFβ signaling
KW  - retina
KW  - retinitis pigmentosa
KW  - neuro-/photoreceptor degeneration
KW  - MAP kinase pathway
KW  - ferroptosis
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283971
SN  - 1422-0067
VL  - 23
IS  - 5
ER  - 
TY  - JOUR
A1  - Schlecht, Anja
A1  - Vallon, Mario
A1  - Wagner, Nicole
A1  - Ergün, Süleyman
A1  - Braunger, Barbara M.
T1  - TGFβ-Neurotrophin Interactions in Heart, Retina, and Brain
JF  - Biomolecules
N2  - Ischemic insults to the heart and brain, i.e., myocardial and cerebral infarction, respectively, are amongst the leading causes of death worldwide. While there are therapeutic options to allow reperfusion of ischemic myocardial and brain tissue by reopening obstructed vessels, mitigating primary tissue damage, post-infarction inflammation and tissue remodeling can lead to secondary tissue damage. Similarly, ischemia in retinal tissue is the driving force in the progression of neovascular eye diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD), which eventually lead to functional blindness, if left untreated. Intriguingly, the easily observable retinal blood vessels can be used as a window to the heart and brain to allow judgement of microvascular damages in diseases such as diabetes or hypertension. The complex neuronal and endocrine interactions between heart, retina and brain have also been appreciated in myocardial infarction, ischemic stroke, and retinal diseases. To describe the intimate relationship between the individual tissues, we use the terms heart-brain and brain-retina axis in this review and focus on the role of transforming growth factor β (TGFβ) and neurotrophins in regulation of these axes under physiologic and pathologic conditions. Moreover, we particularly discuss their roles in inflammation and repair following ischemic/neovascular insults. As there is evidence that TGFβ signaling has the potential to regulate expression of neurotrophins, it is tempting to speculate, and is discussed here, that cross-talk between TGFβ and neurotrophin signaling protects cells from harmful and/or damaging events in the heart, retina, and brain.
KW  - heart-brain axis
KW  - brain-retina axis
KW  - neurotrophins
KW  - TGFβ signaling
KW  - myocardial infarction
KW  - diabetic retinopathy
KW  - age-related macular degeneration
KW  - ischemic stroke
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246159
SN  - 2218-273X
VL  - 11
IS  - 9
ER  -