Abstract
Purpose :
Aniridia is a devastating panocular eye disease that affects 1 in every 50,000 to 100,000 newborns, typically caused by heterozygous mutations in the PAX6 gene. Patients with aniridia exhibit a diverse range of ocular abnormalities, each to differing extents, including corneal opacification, cataract, optic nerve hypoplasia, and foveal hypoplasia. Little is known about how the disease impacts retinal health during early development. We performed a series of in vivo assessments of retinal health and visual function and tracked their changes in aniridia mice.
Methods :
We used the Pax6Sey+/- mouse model of aniridia, as it possesses a nonsense mutation identical to those in most cases of human aniridia. We whole mounted 15 retinas in 4 key age groups (P10, P60, P100, P200) and immunostained them with markers such as SMI-32 for subtype RGCs and DAPI for nuclei of retinal cells. 6 retinal sagittal sections were also examined to assess changes in retinal layer structures. Intraocular pressure (IOP) was measured regularly using rebound tonometry to monitor glaucomatous damage which is a common symptom of aniridia. Visual behavior was monitored using the qOMR system which projects a virtual cylinder with moving black and white bars. The subject’s innate ability to perceive the movement of these bars at varying frequencies measure their visual acuity. Finally, we used visible-light optical coherence tomography (Vis-OCT), an imaging technique with post imaging data analysis established by our laboratories, to examine cross-sectional and en face retinal scans in vivo.
Results :
IOP was found to increase with age in Pax6Sey+/- mice, averaging ~25mmHg as opposed to ~15mmHg in WT mice. Visual acuity measurements confirm that this visual deficit continues to worsen with age. The mean acuity for WT mice was 0.41 ±0.02cyc/deg, while the mean acuity for Pax6Sey+/- was 0.21 ±0.05 cyc/deg. Confocal imaging of flat-mount retinas and retinal sections confirmed that the retina continues to degrade with age in Pax6Sey+/- mice. Our initial vis-OCT imaging data also confirms that retinal structure is impaired in Pax6Sey+/-, particularly in the optic nerve head.
Conclusions :
Our data shows that neural damage and vision deteriorates with age in Pax6Sey+/- mice. The combination of in vivo assessments makes it possible to track changes in individuals, which enables a better understanding of retinal developmental defects in aniridia.
This is a 2021 ARVO Annual Meeting abstract.