远程预处理可预防视网膜脱离导致的视网膜细胞死亡。
Remote Preconditioning Provides Protection Against Retinal Cell Death From Retinal Detachment.
作者信息
Scavuzzi Bruna Miglioranza, Shanmugam Sumathi, Yang Mengling, Yao Jingyu, Hager Heather, Kaur Bhavneet, Jia Lin, Abcouwer Steven F, Zacks David N
机构信息
Department of Ophthalmology and Visual Sciences, Michigan Medicine, Kellogg Eye Center, University of Michigan, Ann Arbor, Michigan, United States.
出版信息
Invest Ophthalmol Vis Sci. 2025 Feb 3;66(2):34. doi: 10.1167/iovs.66.2.34.
PURPOSE
Remote preconditioning involves injury to a tissue that results in protection to a subsequent injury in a distal tissue. Here, we investigated the impact of remote preconditioning on retinal detachment (RD) injury, hypothesizing that a previous contralateral RD would protect the fellow retina against inflammation and cell death following its detachment.
METHODS
RD was created in adult C57BL/6J mice with subretinal sodium hyaluronate injection. Preconditioning involved RD in the right eye at 1, 3, 7, or 28 days before left eye detachment, whereas the control group only received RD to the left eye. Retinas were harvested 24 hours post-left eye detachment in both groups. Cell death was assessed using Cell Death Detection ELISA and mRNA expression was evaluated via qRT-PCR.
RESULTS
Contralateral RD promoted a transient protection against retinal cell death from 1 to 3 days and waned by 7 days compared with control RD retinas with intact fellow retinas. Contralateral RD significantly protected against post-RD cell death (P = 0.0002) and caspase 3 cleavage (P = 0.0449), compared with control RD retinas with intact fellow retinas 1-day post-RD. Detached fellow retinas from the preconditioning group expressed significantly less Tnfa (P = 0.0066), Cxcl10 (P = 0.0099), and Fas (P = 0.0223) mRNAs, compared with the detached retinas of the control group. In contrast, upregulation of type-I-IFN pathway genes, including Irf7 (P = 0.0106) and Ifit1 (P = 0.0740), following RD was higher in the preconditioning group.
CONCLUSIONS
RD in one eye produces a transient remote preconditioning effect that protects the fellow retina against retinal cell death following subsequent RD.
目的
远程预处理涉及对一个组织造成损伤,从而对远处组织的后续损伤产生保护作用。在此,我们研究了远程预处理对视网膜脱离(RD)损伤的影响,假设先前的对侧RD会保护健侧视网膜在脱离后免受炎症和细胞死亡的影响。
方法
通过玻璃体腔注射透明质酸钠在成年C57BL/6J小鼠中造成RD。预处理包括在左眼脱离前1、3、7或28天对右眼进行RD,而对照组仅对左眼进行RD。两组均在左眼脱离后24小时收获视网膜。使用细胞死亡检测ELISA评估细胞死亡,并通过qRT-PCR评估mRNA表达。
结果
与健侧视网膜完整的对照RD视网膜相比,对侧RD在1至3天内对视网膜细胞死亡产生短暂保护作用,并在7天时减弱。与健侧视网膜完整的对照RD视网膜在RD后1天相比,对侧RD显著保护免受RD后细胞死亡(P = 0.0002)和半胱天冬酶3裂解(P = 0.0449)。与对照组脱离的视网膜相比,预处理组脱离的健侧视网膜中Tnfa(P = 0.0066)、Cxcl10(P = 0.0099)和Fas(P = 0.0223)mRNA的表达明显减少。相反,预处理组RD后I型干扰素途径基因(包括Irf7(P = 0.0106)和Ifit1(P = 0.0740))的上调更高。
结论
一只眼睛的RD产生短暂的远程预处理效应,可保护健侧视网膜在随后的RD后免受视网膜细胞死亡。