Seasonal Variation in ATP-Induced Retinal Damage in the Cone-Dominant 13-Lined Ground Squirrel

To examine whether time of year (relative to hibernation emergence) influences the retinal degenerative effects of intravitreal injection of adenosine triphosphate (ATP) in the 13-lined ground squirrel (13-LGS).

Eighteen (9 male, 9 female) 13-LGS in three experimental cohorts (early season, mid-season, late season) (n = 6 each) underwent baseline imaging using scanning light ophthalmoscopy (SLO) and optical coherence tomography (OCT). Animals then received a 10-µL intravitreal injection of 0.723 M ATP, followed by OCT and SLO imaging at 3, 10, and 21 days. Adaptive optics SLO (AOSLO) was performed in animals without retinal damage after the 21-day follow-up. Retinal thickness, choroidal thickness, and cone density measures were compared to values from wild-type controls (n = 12).

Five animals (four early season, one late season) showed retinal damage post-ATP injection (Fisher's exact test, P = 0.065). Animals with retinal damage displayed areas of disrupted retinal lamination on OCT. Any changes in OCT thickness were generally present on initial follow-up and resolved at later time points. Follow-up imaging with AOSLO on animals without retinal damage showed no significant differences in the cone mosaic topography from control eyes. Axial length was increased in mid-/late-season cohorts relative to early season (P = 0.0025 and P = 0.0007).

In this pilot study, the 13-LGS appears more susceptible to ATP-induced retinal damage during the early season. Future studies adjusting dose based on ocular biometry may help elucidate the impact of time of year on chemical response.

Consideration of ocular biometry in this and other animal models is merited when using intravitreal methods of chemical administration.