Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development
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Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development. / Günter, Alexander; Sothilingam, Vithiyanjali; Orlich, Michael M; Nordheim, Alfred; Seeliger, Mathias W; Mühlfriedel, Regine.
In: INT J MOL SCI, Vol. 24, No. 16, 09.08.2023, p. 12597.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development
AU - Günter, Alexander
AU - Sothilingam, Vithiyanjali
AU - Orlich, Michael M
AU - Nordheim, Alfred
AU - Seeliger, Mathias W
AU - Mühlfriedel, Regine
PY - 2023/8/9
Y1 - 2023/8/9
N2 - Serum response factor (SRF) controls the expression of muscle contraction and motility genes in mural cells (MCs) of the vasculature. In the retina, MC-SRF is important for correct angiogenesis during development and the continuing maintenance of the vascular tone. The purpose of this study was to provide further insights into the effects of MC SRF deficiency on the vasculature and function of the mature retina in SrfiMCKO mice that carry a MC-specific deletion of Srf. Retinal morphology and vascular integrity were analyzed in vivo via scanning laser ophthalmoscopy (SLO), angiography, and optical coherence tomography (OCT). Retinal function was evaluated with full-field electroretinography (ERG). We found that retinal blood vessels of these mutants exhibited different degrees of morphological and functional alterations. With increasing severity, we found vascular bulging, the formation of arteriovenous (AV) anastomoses, and ultimately, a retinal detachment (RD). The associated irregular retinal blood pressure and flow distribution eventually induced hypoxia, indicated by a negative ERG waveform shape. Further, the high frequency of interocular differences in the phenotype of individual SrfiMCKO mice points to a secondary nature of these developments far downstream of the genetic defect and rather dependent on the local retinal context.
AB - Serum response factor (SRF) controls the expression of muscle contraction and motility genes in mural cells (MCs) of the vasculature. In the retina, MC-SRF is important for correct angiogenesis during development and the continuing maintenance of the vascular tone. The purpose of this study was to provide further insights into the effects of MC SRF deficiency on the vasculature and function of the mature retina in SrfiMCKO mice that carry a MC-specific deletion of Srf. Retinal morphology and vascular integrity were analyzed in vivo via scanning laser ophthalmoscopy (SLO), angiography, and optical coherence tomography (OCT). Retinal function was evaluated with full-field electroretinography (ERG). We found that retinal blood vessels of these mutants exhibited different degrees of morphological and functional alterations. With increasing severity, we found vascular bulging, the formation of arteriovenous (AV) anastomoses, and ultimately, a retinal detachment (RD). The associated irregular retinal blood pressure and flow distribution eventually induced hypoxia, indicated by a negative ERG waveform shape. Further, the high frequency of interocular differences in the phenotype of individual SrfiMCKO mice points to a secondary nature of these developments far downstream of the genetic defect and rather dependent on the local retinal context.
KW - Animals
KW - Mice
KW - Serum Response Factor/genetics
KW - Retinal Detachment
KW - Retina
KW - Retinal Vessels
KW - Angiography
U2 - 10.3390/ijms241612597
DO - 10.3390/ijms241612597
M3 - SCORING: Journal article
C2 - 37628776
VL - 24
SP - 12597
JO - INT J MOL SCI
JF - INT J MOL SCI
SN - 1661-6596
IS - 16
ER -