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使用慢性眼高压大鼠模型对自噬在视网膜神经节细胞存活中的作用进行时间特征分析。

Characterization of the role of autophagy in retinal ganglion cell survival over time using a rat model of chronic ocular hypertension.

机构信息

Department of Ophthalmology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea.

Department of Ophthalmology, Soonchunhyang University Hospital Bucheon, 170 Jomaru-ro, Wonmi-gu, Bucheon, 14584, Republic of Korea.

出版信息

Sci Rep. 2021 Mar 11;11(1):5767. doi: 10.1038/s41598-021-85181-x.

DOI:10.1038/s41598-021-85181-x
PMID:33707562
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7952572/
Abstract

Autophagy is an essential cellular process for the degradation and recycling of cellular components, and its dysregulation has been linked to neuronal cell death and neurodegeneration. In glaucoma, the role of autophagy in retinal ganglion cell (RGC) survival remains contradictory. Moreover, the effects of autophagy modulation at different time-points on RGC survival in a glaucoma model have not been investigated. In this study, we assessed the time-dependent role of autophagy in RGC survival in a circumlimbal suture-induced ocular hypertensive (OHT) rat model. Intraocular pressure (IOP) elevation led to a gradual autophagy induction, which reached a maximum between 1 and 4 weeks after OHT induction. On the other hand, early autophagy was impaired between 1 and 3 days after circumlimbal suturing, indicated by increased p62 levels due to reduced autophagosomal turnover. The intravitreal administration of rapamycin at different time-points after the application of the circumlimbal suture indicated that autophagy induction early during OHT development had potent survival-promoting effects in RGCs. In conclusion, our findings suggest that the role of autophagy in RGCs during OHT development might differ in a time-dependent manner. Modulating autophagy at the appropriate time might serve as a potential therapeutic approach to enhance RGC survival in OHT.

摘要

自噬是细胞降解和回收细胞成分的必要过程，其失调与神经元细胞死亡和神经退行性变有关。在青光眼，自噬在视网膜神经节细胞 (RGC) 存活中的作用仍然存在争议。此外，在青光眼模型中，自噬调节在不同时间点对 RGC 存活的影响尚未被研究。在这项研究中，我们评估了自噬在环扎缝线诱导的眼高压 (OHT) 大鼠模型中对 RGC 存活的时间依赖性作用。眼内压升高导致自噬逐渐诱导，在 OHT 诱导后 1 至 4 周达到最大值。另一方面，在环扎缝线后 1 至 3 天，早期自噬受到损害，这是由于自噬体周转率降低导致 p62 水平增加所致。在环扎缝线应用后不同时间点玻璃体腔内给予雷帕霉素表明，在 OHT 发展早期诱导的自噬对 RGC 具有强烈的生存促进作用。总之，我们的研究结果表明，自噬在 OHT 发展过程中对 RGC 的作用可能随时间而不同。在适当的时间调节自噬可能是增强 OHT 中 RGC 存活的一种潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/3fb51350ba5d/41598_2021_85181_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/d21d971c60f0/41598_2021_85181_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/89e07089bb20/41598_2021_85181_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/6652cadc0cbb/41598_2021_85181_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/a28ff6a6ddb4/41598_2021_85181_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/180e6515e7c3/41598_2021_85181_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/ca24bcd02cd4/41598_2021_85181_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/3fb51350ba5d/41598_2021_85181_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/d21d971c60f0/41598_2021_85181_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/89e07089bb20/41598_2021_85181_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/14bcb2d9a0e6/41598_2021_85181_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/6652cadc0cbb/41598_2021_85181_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/a28ff6a6ddb4/41598_2021_85181_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/180e6515e7c3/41598_2021_85181_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/ca24bcd02cd4/41598_2021_85181_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd49/7952572/3fb51350ba5d/41598_2021_85181_Fig8_HTML.jpg

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