Protecting Neural Circuitry After Injury
Abstract
Blast-related injuries can result in retinal detachment (RD). RD causes separation of the neural retina from the retinal pigmented epithelium and uncouples photoreceptors from their synaptic partners, ultimately leading to blindness. We discovered that synaptic damage is due in part to an increase in the activity of Rho kinase (ROCK). We proposed therefore to prevent the disruption to retinal synaptic circuitry after injury by using a highly efficacious ROCK inhibitor, AR13503. The work is done on adult pigs, whose retina is similar to humans, to increase the translational potential of the results. Our results on the protection of rod synapses with AR13503 have been published. This year we primarily focused on cone synapses. We found that cone ribbons shorten dramatically after detachment and that synaptic invaginations flatten. These disruptive changes can be prevented with ROCK inhibition by intravitreal injection of AR13503. The drug is effective whether applied at the time of detachment or after a delay of 2 hrs. Thus it could be applied at the time of an iatrogenic detachment, as done for gene therapy or stem cell transplants, as well as shortly after a blast injury. After reattachment, cone synaptic morphology appears normal however ERG responses for cone vision are abnormal. Application of drug improves function. ROCK inhibition protects both rod and cone synapses from injury over time and could help preserve vision for individuals who suffer trauma.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1201621
Entities
People
- Ellen Townes-anderson
Organizations
- New Jersey Medical School