Investigating the role of Caspase-1 in a mouse model of Juvenile X-linked Retinoschisis.

Purpose: Previous studies have reported Caspase-1 () is upregulated in mouse models of Juvenile X-linked Retinoschisis (XLRS), however no functional role for in disease progression has been identified. We performed electroretinogram (ERG) and standardized optical coherence tomography (OCT) in mice deficient in the Retinoschisin-1 () and and Caspase-11 genes (-KO ) to test the hypothesis that may play a role in disease evolution and or severity of disease. Currently, no studies have ventured to investigate the longer-term effects of on phenotypic severity and disease progression over time in XLRS, and specifically the effect on electroretinogram.

Methods: -KO; mice were generated by breeding -KO mice with mice. OCT imaging was analyzed at 2-, 4-, and 15-16 months of age. Outer nuclear layer (ONL) thickness and adapted standardized cyst severity score were measured and averaged from 4 locations 500 μm from the optic nerve. Adapted standardized cyst severity score was 1: absent cysts, 2: <30 μm, 3: 30-49 μm, 4: 50-69 μm, 5: 70-99 μm, 6: >99 μm. Electroretinograms (ERG) were recorded in dark-adapted and light-adapted conditions at 2 and 4 months. Results obtained from -KO and -KO; eyes were compared with age matched WT control eyes at 2 months.

Results: Intraretinal schisis was not observed on OCT in WT eyes, while schisis was apparent in most -KO and -KO; eyes at 2 and 4 months of age. There was no difference in the cyst severity score from 2 to 4 months of age, or ONL thickness from 2 to 16 months of age between -KO and -KO; eyes. ERG amplitudes were similarly reduced in -KO and -KO; compared to WT controls at 2 months of age, and there was no difference between KO and -KO; eyes at 2 or 4 months of age, suggesting no impact on the electrical function of photoreceptors over time in the absence of .

Conclusion: Although has been reported to be significantly upregulated in KO mice, our preliminary data suggest that removing does not modulate photoreceptor electrical function or alter the trajectory of the retinal architecture over time.