| Autor: |
Townes-Anderson E; Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA., Halász É; Department of Pharmacology, Physiology and Neuroscience, Rutgers New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA., Sugino I; Institute of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, 90 Bergen Street, Newark, NJ 07103, USA., Davidow AL; Department of Biostatistics, New York University School of Global Public Health, 708 Broadway, New York, NY 10003, USA., Frishman LJ; Department of Vision Sciences, College of Optometry, University of Houston, Martin Luther King Blvd, Houston, TX 77204, USA., Fritzky L; Cellular Imaging and Histology Core, Rutgers New Jersey Medical School, 205 South Orange Avenue, Newark, NJ 07103, USA., Yousufzai FAK; Cellular Imaging and Histology Core, Rutgers New Jersey Medical School, 205 South Orange Avenue, Newark, NJ 07103, USA., Zarbin M; Institute of Ophthalmology and Visual Science, Rutgers New Jersey Medical School, 90 Bergen Street, Newark, NJ 07103, USA. |
| Abstrakt: |
Attachment of a detached retina does not always restore vision to pre-injury levels, even if the attachment is anatomically successful. The problem is due in part to long-term damage to photoreceptor synapses. Previously, we reported on damage to rod synapses and synaptic protection using a Rho kinase (ROCK) inhibitor (AR13503) after retinal detachment (RD). This report documents the effects of detachment, reattachment, and protection by ROCK inhibition on cone synapses. Conventional confocal and stimulated emission depletion (STED) microscopy were used for morphological assessment and electroretinograms for functional analysis of an adult pig model of RD. RDs were examined 2 and 4 h after injury or two days later when spontaneous reattachment had occurred. Cone pedicles respond differently than rod spherules. They lose their synaptic ribbons, reduce invaginations, and change their shape. ROCK inhibition protects against these structural abnormalities whether the inhibitor is applied immediately or 2 h after the RD. Functional restoration of the photopic b-wave, indicating cone-bipolar neurotransmission, is also improved with ROCK inhibition. Successful protection of both rod and cone synapses with AR13503 suggests this drug will (1) be a useful adjunct to subretinal administration of gene or stem cell therapies and (2) improve recovery of the injured retina when treatment is delayed. |
