Dynamics of Retinal Pathology in BALB/cJ Mice Housed in Cyclic Light Conditions: An Imaging Study to Elucidate Changes Induced by Long Term Exposure

Abstract

Purpose: BALB/cJ mice housed in a vivarium exhibited profound retinal abnormalities as a result of standard cyclic lighting conditions (Bell et al 2012). To further explore the influence of environmental illuminance levels on these abnormalities, a cohort of mice were followed by Scanning Laser Ophthalmoscopy (SLO) and Spectral-Domain Optical Coherence Tomography (OCT).

Methods: Mice (n=43) were reared in low illuminance (<10 lx), cyclic light conditions. Baseline imaging (~P70) was performed to screen for pre-existing abnormalities and establish initial morphological levels. Mice were separated into groups (A, B, C) and placed on bottom (Groups A & B) or top rows (Group C) of the cage rack to induce exposure conditions of ~5 & 150 lx, respectively. Experimental groups B & C were periodically imaged multiple times over a 1 year period. Mice from group A (controls) were imaged only once post-baseline at various time points for comparison to groups B & C. SLO and OCT retinal findings (count & ONL morphology) were quantified manually and the resulting trends displayed as a function of time.

Results: Imaging was highly sensitive to changes occurring in the outer retina as a result of chronic light exposure. A small number of retinal lesions and autofluorescent foci (AFF) were visible by infrared and autofluorescence SLO imaging at baseline. Lesions and AFF were identified as photoreceptor layer infoldings (IF) and recruited microglia/macrophages (MM), respectively. Retinal IF were first to be visualized and then followed by punctate autofluorescent MM. Both findings were colocalized suggesting a strong interrelationship. The incidence of these pathology hallmarks increased in all groups (Group A: IF~2.5x/MM~2.5x, B: IF~12x/MM~25x, C: IF~70x, MM~200x) relative to baseline. OCT imaging revealed thinning of the ONL in all groups at 1 year (Group A ~ 11%, B~11%, C~37%) relative to baseline. ONL thinning followed an exponential rate of change but the decay constant varied depending on row position/exposure magnitude (Group A & B = .002, C = .01).

Conclusions: Prolonged exposure to top row illuminance conditions resulted in significant photoreceptor cell loss. Significant retinal degeneration was preceded by both retinal infoldings and recruitment of activated microglia, which suggests these findings are early indicators of light stress in the BALB/cJ model.

Keywords: 689 retina: distal (photoreceptors, horizontal cells, bipolar cells) • 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • 494 degenerations/dystrophies