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  - Wolf, Julian
A1  - Boneva, Stefaniya
A1  - Prinz, Gabriele
A1  - Braunger, Barbara M.
A1  - Wieghofer, Peter
A1  - Agostini, Hansjürgen
A1  - Schlunck, Günther
A1  - Lange, Clemens
T1  - Transcriptional and distributional profiling of microglia in retinal angiomatous proliferation
JF  - International Journal of Molecular Sciences
N2  - Macular neovascularization type 3, formerly known as retinal angiomatous proliferation (RAP), is a hallmark of age-related macular degeneration and is associated with an accumulation of myeloid cells, such as microglia (MG) and infiltrating blood-derived macrophages (MAC). However, the contribution of MG and MAC to the myeloid cell pool at RAP sites and their exact functions remain unknown. In this study, we combined a microglia-specific reporter mouse line with a mouse model for RAP to identify the contribution of MG and MAC to myeloid cell accumulation at RAP and determined the transcriptional profile of MG using RNA sequencing. We found that MG are the most abundant myeloid cell population around RAP, whereas MAC are rarely, if ever, associated with late stages of RAP. RNA sequencing of RAP-associated MG showed that differentially expressed genes mainly contribute to immune-associated processes, including chemotaxis and migration in early RAP and proliferative capacity in late RAP, which was confirmed by immunohistochemistry. Interestingly, MG upregulated only a few angiomodulatory factors, suggesting a rather low angiogenic potential. In summary, we showed that MG are the dominant myeloid cell population at RAP sites. Moreover, MG significantly altered their transcriptional profile during RAP formation, activating immune-associated processes and exhibiting enhanced proliferation, however, without showing substantial upregulation of angiomodulatory factors.
KW  - AMD
KW  - Mactel 2
KW  - macular neovascularization
KW  - MNV type 3
KW  - retinal angiomatous proliferation
KW  - RAP
KW  - microglia
KW  - RNA sequencing
KW  - Cx3cr1
KW  - CreERT2
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284072
SN  - 1422-0067
VL  - 23
IS  - 7
ER  -