Establishing Preclinical Quantitative Parameters for Future Assessment of Corneal and Retinal Therapeutics for Aniridia.

Purpose: Aniridia is a rare congenital-blinding disorder caused by pathogenic variants in PAX6 for which there is no vision-saving treatment. Here we aim to deliver quantitative mouse data sufficient to provide preclinical testing of therapeutic approaches to aniridia with reliable power calculations. Methods: We histologically quantify the peripheral thickness of the cornea, retina, and their sublayers in the B6129F1-Sey mouse model of aniridia, using the largest cohort of Wt and Sey mice to date (67 mice, 134 eyes). Results: We show a highly significant thinning of the total cornea and the corneal epithelium. However, the corneal stromal-endothelial layer thickness was unaffected by Sey. Nevertheless, the epithelium and stromal-endothelial layer thickness were highly significantly correlated in Sey mice only. We also show a highly significant thinning of the total retina, and a very-to-highly, significant thinning of the ganglion cell layer (GCL), inner nuclear layer (INL), and outer nuclear layer (ONL) sublayers. In the retina, we found that the GCL layer thickness was very significantly correlated with the ONL and INL thickness, in Sey mice only. Using the data generated here, we calculated the number of mice needed to demonstrate a full or partial correction of the Sey aniridic phenotype. For example, at 80% power a 50% effect will require: for the epithelium, 21 Wt and 21 Sey mice; total cornea, 58 Wt and 58 Sey mice; and total retina, 28 Wt and 28 Sey mice. Conclusions: We deliver quantitative mouse data, which provides preclinical research testing of therapeutic approaches with the information needed to make reliable power calculations.