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MNU诱导的视网膜色素变性模型中疾病进程的新型时空特征

A Novelly-Spatiotemporal Characterization of the Disease Course in the MNU-Induced Retinitis Pigmentosa Model.

作者信息

Yan Weiming, He Qiurui, Long Pan, Zhang Lei, Wang Haiyan, Chen Tao

机构信息

Department of Ophthalmology, Fuzong Clinical Medical College of Fujian Medical University, Dongfang Hospital Affiliated to Xiamen University, Fuzhou, People's Republic of China.

Department of Cardiovascular Intervention, The Third Hospital of Zhangzhou, Zhangzhou, People's Republic of China.

出版信息

J Inflamm Res. 2024 Nov 20;17:9243-9254. doi: 10.2147/JIR.S474102. eCollection 2024.

DOI:10.2147/JIR.S474102
PMID:39583858
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11586005/
Abstract

OBJECTIVE

With the aids of ophthalmic imaging techniques for animals, the spatiotemporal characterization of MNU-induced retinitis pigmentosa (RP) rats were performed.

METHODS

Sprague-Dawley (SD) rats were randomly divided into normal group (N), MNU-low-dose group (L) and MNU-high-dose group (H). Rats in the L and H group were given intraperitoneally injection with 40 and 60 mg/kg of MNU, a kind of alkylating agent, respectively. The body weight, electroretinogram (ERG) and retinal structure were observed on day one (D1), D3, and D7 after MNU administration. FFA, OCT, TUNEL staining, and immunostaining of Iba1 were also performed.

RESULTS

After MNU injection, the weight and ERG amplitudes of rats in both L and H groups decreased gradually, compared to those of the normal group ( 0.05). Fundus imaging revealed enlargement of the optical disc and slightly reduced shadow of retinal vessels in both L and H groups, which were more obvious on D7. No significant morphological changes of retinal vessels were found under FFA. OCT and retinal histological examination revealed that outer nuclear layers (ONL) became thinner gradually in both L and H groups, and disappeared in H group at D7. MNU administration increased the numbers of apoptotic cells and Iba1-positive cells in the retinas gradually, showing a dose-dependent effect.

CONCLUSION

MNU gradually reduced the ONL thickness and the ERG amplitudes in the MNU-induced RP model revealed by various ophthalmic imaging techniques, along with the increased apoptosis of photoreceptors, the microglia cells activation, which provide indicators for new intervention effect for RP.

摘要

目的

借助动物眼科成像技术,对N-甲基-N-亚硝基脲(MNU)诱导的视网膜色素变性(RP)大鼠进行时空特征分析。

方法

将Sprague-Dawley(SD)大鼠随机分为正常组(N)、MNU低剂量组(L)和MNU高剂量组(H)。L组和H组大鼠分别腹腔注射40和60mg/kg的MNU(一种烷化剂)。在给予MNU后的第1天(D1)、第3天和第7天观察大鼠体重、视网膜电图(ERG)和视网膜结构。还进行了荧光素眼底血管造影(FFA)、光学相干断层扫描(OCT)、TUNEL染色和离子钙结合衔接分子1(Iba1)免疫染色。

结果

注射MNU后,L组和H组大鼠的体重和ERG振幅均逐渐下降,与正常组相比差异有统计学意义(P<0.05)。眼底成像显示L组和H组视盘均增大,视网膜血管阴影略有减小,在D7时更为明显。FFA下未发现视网膜血管有明显形态学改变。OCT和视网膜组织学检查显示,L组和H组外核层(ONL)均逐渐变薄,H组在D7时消失。给予MNU后,视网膜中凋亡细胞和Iba1阳性细胞数量逐渐增加,呈剂量依赖性效应。

结论

多种眼科成像技术显示,在MNU诱导的RP模型中,MNU逐渐降低ONL厚度和ERG振幅,同时光感受器凋亡增加,小胶质细胞活化,为RP新的干预效果提供了指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/034539a3868a/JIR-17-9243-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/4b5fb0074e53/JIR-17-9243-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/5a05401e6702/JIR-17-9243-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/7ad2019fcd2a/JIR-17-9243-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/d48b579f6327/JIR-17-9243-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/3e743ed599de/JIR-17-9243-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/c8369fd0ed65/JIR-17-9243-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/034539a3868a/JIR-17-9243-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/4b5fb0074e53/JIR-17-9243-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/5a05401e6702/JIR-17-9243-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/7ad2019fcd2a/JIR-17-9243-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/d48b579f6327/JIR-17-9243-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/3e743ed599de/JIR-17-9243-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/c8369fd0ed65/JIR-17-9243-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f04/11586005/034539a3868a/JIR-17-9243-g0007.jpg

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