Rouen Université Institut National de la Santé et de la Recherche Médicale Unité 1245, Genomic and Personalized Medicine in Cancer and Neurological Disorders, Institute for Research and Innovation in Biomedicine (IRIB), Normandie University, 76183, Rouen, France.
Regional Platform for Cell Imaging of Normandy (PRIMACEN), Institute for Research and Innovation in Biomedicine (IRIB), Rouen University, 76183, Rouen, France.
eNeuro. 2023 Apr 26;10(4). doi: 10.1523/ENEURO.0295-22.2022. Print 2023 Apr.
In addition to brain disorders, which constitute a devastating consequence of prenatal alcohol exposure (PAE), eye development is also significantly affected. Given that the retina is a readily accessible part of the central nervous system, a better understanding of the impact of ethanol on retinal development might provide ophthalmological landmarks helpful for early diagnosis of fetal alcohol syndrome. This study aimed to provide a fine morphometric and cellular characterization of the development of retinal microvasculature and neurovascular interactions in a mouse model of fetal alcohol spectrum disorder (FASD). The data revealed that PAE impaired superficial vascular plexus development. In particular, progression of the vascular migration front was significantly decreased in PAE retinas, supporting a delay in plexus progression. Moreover, a significant decrease in the vessel density and number of perforating vessels was quantified in PAE mice, supporting less angiogenesis. The present study provides also the first evidence of a close interaction between migrating calretinin-positive interneurons and perforating microvessels in the inner nuclear layer of the developing retina. This neurovascular association was significantly impaired by PAE. Moreover, projections of amacrine cells were abnormally distributed and densified in stratum S1 and S2. In humans, comparison of a five-month-old control infant with a three-month-old alcohol-exposed case revealed a similar mispositioning of calretinin-positive interneurons. This opens new research avenues regarding a neurovascular contribution in the deleterious effects of alcohol in the developing retina and support that ophthalmological examination could become a promising approach for early detection of alcohol-exposed infants presenting with neurovascular brain defects.
除了构成产前酒精暴露（PAE）的毁灭性后果的大脑紊乱之外，眼睛发育也受到显著影响。鉴于视网膜是中枢神经系统的一个易于接近的部分，对乙醇对视网膜发育的影响有更好的理解可能为胎儿酒精综合征的早期诊断提供有帮助的眼科标志。本研究旨在提供胎儿酒精谱系障碍（FASD）小鼠模型中视网膜微血管和神经血管相互作用发育的精细形态计量和细胞特征。研究数据显示，PAE 损害了浅层血管丛的发育。特别是，PAE 视网膜中血管迁移前沿的进展明显减少，支持丛状进展的延迟。此外，在 PAE 小鼠中定量检测到血管密度和穿通血管数量显著减少，支持血管生成减少。本研究还首次提供了证据表明，在发育中的视网膜内层核层中，迁移的 calretinin 阳性中间神经元与穿通微血管之间存在密切的相互作用。这种神经血管的关联因 PAE 而受到严重损害。此外，无长突细胞的投射在 S1 和 S2 层中异常分布和密集。在人类中，将五个月大的对照婴儿与三个月大的酒精暴露病例进行比较，发现 calretinin 阳性中间神经元的位置也存在类似的错位。这为酒精在发育中的视网膜中的神经血管毒性作用的研究开辟了新的途径，并支持眼科检查可能成为检测有神经血管脑缺陷的酒精暴露婴儿的一种有前途的方法。
