Remote Preconditioning Provides Protection Against Retinal Cell Death From Retinal Detachment.

Abstract

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.