Abstract
Purpose: :
To utilize pupillary light response as a measure of restored retinal function following AAV mediated gene transfer of PDEβ6 to the rd10-/- mouse retina under normal diurnal light conditions.
Methods: :
Several cohorts of rd10-/- mice received unilateral subretinal injections of 1ul AAV.CMV.PDEβ. The contralateral eye was used as a non-injected control. Animals were maintained on a 12-hour light/12-hour dark cycle for the duration of testing. Three weeks following injection, pupillary light response measurements were initiated to assess retinal health and potential recovery of retinal function. Pupillometry was performed at regular intervals until week 11. Three separate light intensities were used at each time point.
Results: :
At postnatal day (P) 21, treated eyes showed significant increases in pupillary constriction at all light intensities compared to untreated eyes, as well as substantial decreases in response latency with low light stimuli. These trends were maintained through P70. Control eyes did not show pupillary light responses at low light levels and universally exhibited lower pupillary constriction amplitudes when compared to injected eyes.
Conclusions: :
These results demonstrate that early neonatal administration of AAV.CMV.PDEβ can slow retinal degeneration in the rd10-/- mouse, as evidenced by preservation of the pupillary light reflex. This data serves as an important foundation for subsequent studies exploring long-term rescue of retinal function by AAV medicated gene transfer in rd10-/- mice. Further visual behavior assessments and immunohistochemistry will be performed.
Keywords: gene transfer/gene therapy • retinal degenerations: cell biology • pupillary reflex