Division of Ocular Neurodegeneration, Institute for Ophthalmic Research, University of Tübingen, 72076 Tübingen, Germany.
Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, 75185 Uppsala, Sweden.
Int J Mol Sci. 2023 Aug 9;24(16):12597. doi: 10.3390/ijms241612597.
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 mice that carry a MC-specific deletion of . 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 mice points to a secondary nature of these developments far downstream of the genetic defect and rather dependent on the local retinal context.
血清反应因子（SRF）控制着血管壁细胞（MCs）中肌肉收缩和运动基因的表达。在视网膜中，MC-SRF 对于发育过程中正确的血管生成和血管张力的持续维持非常重要。本研究的目的是进一步了解 MC 特异性缺失 对成熟视网膜血管和功能的影响。通过扫描激光检眼镜（SLO）、血管造影和光相干断层扫描（OCT）在体内分析视网膜形态和血管完整性。通过全视野视网膜电图（ERG）评估视网膜功能。我们发现这些突变体的视网膜血管表现出不同程度的形态和功能改变。随着严重程度的增加，我们发现血管膨出、动静脉（AV）吻合的形成，最终导致视网膜脱离（RD）。相关的视网膜血压和血流分布的不规则最终导致了缺氧，这表现为 ERG 波形的负向。此外，个别 小鼠眼部之间表型的高度差异表明这些发展是遗传缺陷的下游继发性的，而不是依赖于局部视网膜环境。
