Specific deficits in visual electrophysiology without retinal cellular apoptosis in a mouse model of dominant optic atrophy

Abstract

Abstract Purpose Autosomal dominant optic atrophy (ADOA) due to mutations in OPA1 is a slowly progressive optic neuropathy. OPA1 is ubiquitously expressed and plays a key role in mitochondrial fusion. Heterozygous Opa1 mutant mice (B6;C3‐Opa1Q285STOP), with previously reported visual defects and optic nerve changes, were assessed for retinal sequelae. Methods ERGs and VEPs were recorded in 12 month old B6;C3‐Opa1Q285STOP mice (n=4) and age/sex matched wildtype littermate controls. Full scotopic and photopic intensity series were recorded in response to brief (4 ms) single flash stimuli delivered in a ganzfeld dome. End‐organ evidence for apoptosis was explored on TUNEL stained retinal sections. Results Quantification of the major ERG components (a‐wave and b‐wave) confirmed no detectable difference in the amplitude or implicit time of scotopic ERGs across the full intensity range tested. This was also true for the VEP components. Quantification of the photopic ERG responses revealed a significant reduction in the PhNR amplitude in Opa1+/‐ animals relative to wildtypes at the brightest intensity tested. The photopic VEP was also abnormal in mutant mice. There was no increased apoptosis in retinal sections from mutant animals. Conclusion Opa1+/‐ mice display a functional deficit on electrophysiology that is indicative of specific ganglion cell dysfunction. Despite a 50% reduction in Opa1 protein there does not appear to be a significant increase in apoptosis in the retina. This suggests that the protein truncating mutation in this model may lead to RGC dysfunction without triggering RGC death.