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Protecting Neural Circuitry After Injury

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[Technical Report, Annual Report]

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Blast-related injuries can result in retinal detachment RD. RD causes a separation of the neural retina from the retinal pigmented epithelium, uncouples photoreceptors from their synaptic partners, and ultimately leads to blindness. We discovered that synaptic disjunction by photoreceptors is due in part to an increase in the activity of Rho kinase ROCK. We proposed therefore to prevent the damage 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. This past year we extended the time frame of our examination of the ROCK inhibitor by looking at retinas one week after detachment. Drug treated retina appeared to have both better rod synaptic morphology as well as function, as tested by ERGs, than untreated retina after a week. Our work this past year however was primarily focused on cone synapses. Cone synaptic ribbons shorten and disappear with detachment within 2 hours. This damage is prevented by ROCK inhibition. Two days after detachment and spontaneous reattachment, cone synapses look as though they have recovered, however ERG recordings still indicate cone dysfunction. The same result is apparent after one week normal cone synaptic morphology but abnormal function. This year we also examined delayed treatment. Delaying injection of AR13503 for 2hrs after a detachment still promotes reduction of damage to both rod and cone synapses. This is important for a transition of our findings to clinical practice, as it allows for treatment of soldiers and civilians who cannot be treated immediately after injury. We will finalize analysis of ROCK inhibition of cone synaptic damage this year and look forward to summarizing our work on both rod and cone synaptic trauma.


Subject Categories:

  • Medicine and Medical Research
  • Anatomy and Physiology

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[A, Approved For Public Release]