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早期接触西方饮食会加剧雌性小鼠的视觉损伤。

Early exposure to Western Diet exacerbates visual outcomes in female mice.

作者信息

Meseguer David, Furtado Jessica, Zapadka Thomas, Rodriguez Amanda, Na Daxiang, Grajales-Reyes Jose G, Demb Jonathan, Eichmann Anne, Schneeberger Marc

机构信息

Laboratory of Neurovascular Control of Homeostasis, Department of Cellular and Molecular Physiology, Yale School of Medicine, New Haven, CT, USA.

Cardiovascular Research Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.

出版信息

bioRxiv. 2024 Dec 3:2024.11.27.625688. doi: 10.1101/2024.11.27.625688.

Abstract

Obesity, a growing pandemic in Western societies, significantly impacts metabolic health and contributes to visual disorders. While the systemic consequences of obesity, such as chronic inflammation and insulin resistance, are well-studied in adults, its early-life effects on retinal health remain underexplored. Using a maternal Western Diet (WD) exposure model, we investigated the developmental impact of early-life metabolic disturbances on retinal and cognitive function. Our findings reveal that WD exposure from gestation to early adulthood accelerates the onset of features resembling diabetic retinopathy, including increased retinal vascularization, inflammation, and compromised blood-retina barrier integrity, observed within just four months. Females exhibited heightened vulnerability, showing pronounced ocular defects such as anophthalmia, microphthalmia, and congenital cataracts. These results underscore a critical developmental window during which metabolic disruptions predispose to sex-specific retinal and neurovascular pathologies. This work bridges the link between pediatric and adult obesity, highlighting the urgent need for early interventions to mitigate long-term visual impairments that could further impair recognition memory.

摘要

肥胖是西方社会日益严重的流行病,对代谢健康有重大影响,并会导致视觉障碍。虽然肥胖的全身性后果,如慢性炎症和胰岛素抵抗,在成年人中已得到充分研究,但其对视网膜健康的早期影响仍未得到充分探索。我们使用母体西式饮食(WD)暴露模型,研究了早期代谢紊乱对视网膜和认知功能的发育影响。我们的研究结果表明,从妊娠期到成年早期暴露于WD会加速类似糖尿病视网膜病变特征的出现,包括视网膜血管生成增加、炎症以及血视网膜屏障完整性受损,这些在短短四个月内就可观察到。雌性表现出更高的易感性,出现明显的眼部缺陷,如无眼、小眼和先天性白内障。这些结果强调了一个关键的发育窗口期,在此期间代谢紊乱易引发特定性别的视网膜和神经血管病变。这项工作架起了儿童肥胖与成人肥胖之间的桥梁,突出了早期干预以减轻可能进一步损害识别记忆的长期视觉损伤的迫切需求。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/816f/11642743/636be21b3987/nihpp-2024.11.27.625688v1-f0001.jpg

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