Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development

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 -