The Effect And Mechanism Of TRPML1 On Photoreceptor Death In Experimental Retinal Detachment

Objective: Transient receptor potential mucolipin 1(TRPML1)mediates autophagy activation and reactive oxygen species clearance,Loss of function of TRPML1 leads to photoreceptor damage and retinal dystrophy.In this study,we used a rat model of retinal detachment(RD)and an agonist of TRPML1 to investigate the effects of transient receptor potential mucolipin 1(TRPML1)on photoreceptor cells and the underlying mechanism.Methods: Healthy male SD rats were randomly divided into Normal group(Normal),retinal detachment control group(RD),agonist solution control group(DMSO),agonist group(ML-SA1).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 TRPML1 removes excess ROS and attenuates photoreceptor cell apoptosis by activating autophagy.Treatment with ML-SA1 may improve vision recovery in RD.