TRPML1 inhibited photoreceptor apoptosis and protected the retina by activation of autophagy in experimental retinal detachment.

Abstract:

OBJECTIVE:In this study, we used a rat model of retinal detachment (RD) to investigate the effects of transient receptor potential mucolipin 1 (TRPML1) on photoreceptor cells and the underlying mechanism. METHODS:An RD model was established by subretinal injection of sodium hyaluronate, and mucolipin synthetic agonist 1 (ML-SA1) and dimethyl sulfoxide (DMSO) were subretinally injected after RD induction. Retinal morphology was observed using haematoxylin-eosin (HE) staining, and the apoptosis of photoreceptor cells was detected by transmission electron microscopy (TEM). Reactive oxygen species (ROS) were examined with a ROS detection kit. The retinal expression levels of TRPML1, the autophagy-related protein microtubule-associated protein 1 light chain 3 (LC3), Beclin1, and cleaved caspase3 were detected by western blotting. The Morris water maze was used to test vision-dependent behaviour. RESULTS:We found that retinal structure and the outer nuclear layer (ONL) were improved and that the apoptosis of photoreceptor cells was reduced after ML-SA1 injection. The expression of ROS was reduced, and the loss of TRPML1 was inhibited after ML-SA1 treatment. The LC3-II to LC3-I ratio and Beclin1 expression were enhanced, and cleaved caspase3 expression was decreased after ML-SA1 treatment. Treatment with ML-SA1 also improved vision-dependent behaviour. CONCLUSIONS:Our findings suggest that ML-SA1 attenuates photoreceptor apoptosis and improves vision-dependent behavior by activation of autophagy.

journal_name

Ophthalmic Res

journal_title

Ophthalmic research

authors

Yan Y,Wang Y,Ding J,Lu L,Ke G,Dong K

doi

10.1159/000512104

subject

Has Abstract

pub_date

2020-10-07 00:00:00

eissn

0030-3747

issn

1423-0259

pii

000512104

pub_type

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