Abstract
Purpose :
To dissect the mechanism underlying photoreceptor degeneration after retinal detachment.
Methods :
The vitreous from patients with retinal detachment was analyzed by quantitative metabolics. A rat model of retinal detachment and cultured photoreceptors subjected to oxidative stress were also employed to interrogate underlying molecular mechanisms.
Results :
Key metabolites in the glycolytic pathway were dysregulated in the vitreous of patients with retinal detachment. In the animal models, We showed that retinal detachment activated dynamin-related protein 1 dependent mitochondrial fission, ROS release and apoptotic cascades. Pharmacological blockade or RNA interference of dynamin-related protein 1 activity preserved mitochondrial integrity, attenuated ROS production and rescued photoreceptors both in vivo and in vitro.
Conclusions :
Our findings have identified mitochondrial fission as a critical ‘danger signal’ to photoreceptor degeneration and dynamin-related protein 1 as a promising therapeutic target for photoreceptor protection after retinal detachment.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.