The BALB/c mouse: Effect of standard vivarium lighting on retinal pathology during aging

Abstract

BALB/cJ mice housed under normal vivarium lighting conditions can exhibit profound retinal abnormalities, including retinal infoldings, autofluorescent inflammatory cells, and photoreceptor degeneration. To explore the sensitivity of the outer retina to cyclic lighting during aging, a cohort of BALB/cJ mice was evaluated with Scanning Laser Ophthalmoscopy (SLO), Spectral-Domain Optical Coherence Tomography (OCT) and conventional histopathology. Mice were bred and reared in a low-illuminance (extracage/intracage: 13 lx/1 lx) vivarium under cyclic light (14 h light: 10 h dark). Retinal imaging (around postnatal day 70) was performed to screen for any pre-existing abnormalities and to establish a baseline. Mice with normal retinas were separated into groups (A, B, C) and placed on bottom (Groups A & B) or top (Group C) of the cage racks where cage illumination was <10 & 150 lx respectively. Experimental groups B & C were imaged multiple times over a 17 month period. Mice from group A (controls) were imaged only once post-baseline at various times for comparison to groups B & C. Mice were assessed by histology at 8, 15, 20, 36, and 56 weeks and immunohistochemistry at 15 weeks post-baseline. SLO and OCT retinal images were measured and the resulting trends displayed as a function of age and light exposure. Retinal lesions (RL) and autofluorescent foci (AFF) were identified with histology as photoreceptor layer infoldings (IF) and localized microglia/macrophages (MM), respectively. Few RL and AFF were evident at baseline. Retinal infoldings were the earliest changes followed by subjacent punctate autofluorescent MM. The colocalization of IF and MM suggests a causal relationship. The incidence of these pathological features increased in all groups relative to baseline. OCT imaging revealed thinning of the outer nuclear layer (ONL) in all groups at 1 year relative to baseline. ONL thinning followed an exponential rate of change but the decay constant varied depending on intensity of illumination of the groups. Advanced age and top row illuminance conditions resulted in significant photoreceptor cell loss as judged by decreased thickness of the ONL. Photoreceptor loss was preceded by both retinal infoldings and the presence of autofluorescent inflammatory cells in the outer retina, suggesting that these changes are early indicators of light toxicity in the BALB/cJ mouse.

The adult zebrafish retina: In vivo optical sectioning with Confocal Scanning Laser Ophthalmoscopy and Spectral-Domain Optical Coherence Tomography

“…Specific anatomical sites within an animal, whether it is a mammal or fish, can be used to calibrate the instrument focus position (Bell et al, 2015). The VRI and the proximal cone mosaic, areas of significant native contrast within the retina, can be used to establish calibration endpoints.…”

“…Both instruments enable non-invasive, in vivo assessment of ocular tissues from a multitude of animal species. In vivo assessments have previously demonstrated that abnormal phenotypes may arise in both mammals and zebrafish that are present prior to the initiation of experimental studies (Bell et al, 2015; Bell et al, 2012; Joshi et al, 2016; Mattapallil et al, 2012; Tschopp et al, 2010). Using these instruments to screen for baseline abnormalities will avoid the potential for unexpected, confusing and confounding experimental results.…”

“…Many groups have demonstrated the ability to visualize a wide array of unique pathology and/or anatomical features using SLO. Such features include abnormal ocular phenotypes (Chauhan et al, 2012; Samuels et al, 2013), age-related or light induced changes (Bell et al, 2015; Sparrow et al, 2013), vascular angiography (Paques et al, 2006; Seeliger et al, 2005), labeled proteins (Beck et al, 2010; Seeliger et al, 2005), inflammatory cells (Paques et al, 2006), and apoptotic cells (Maass et al, 2007). …”

Vision in laboratory rodents—Tools to measure it and implications for behavioral research

“…For reference, 250 lux is less than recommended for office working conditions by a European Union regulation [156] and 2500 lux could be measured at midday during an overcast day [157]. In fact, albino Balb/C mice and Sprague-Dawley rats have been reported to develop retinal degeneration even under vivarium conditions [18,19]. As albino strains are extremely sensitive for light damage, we strongly suggest housing them in the dimmest part of the laboratory animal facility (for instance, lowest rows of cage racks) whenever possible.…”

“…Albino mice and rats are well known for their poor vision, but they do still respond to visual pattern stimulation [15] and thus likely utilize their vision in a behaviorally meaningful way. However, vision in albino rodents may easily be lost upon acute bright light exposure [16,17], or chronic low light level exposure even at their standard vivarium [18,19].…”