Visual dysfunction and pupillary responses are dissociated in the Opa3 mutant mouse with retinal degeneration

Abstract

AbstractPurpose To assess the affect of the missense mutation p.L122P in a mouse model of 3‐methylglutaconic aciduria (MGA‐III), a neuro‐metabolic syndrome which presents with retinal and optic atrophy and neurological impairment.Methods Visual acuity was quantified in an optokinetic nystagmus drum by increasing the spatial frequency of the grating until an optomotor response could not be elicited. Pupillary light responsiveness was assessed by video pupillometry. Time course and phenotype of retinal degeneration was examined using haematoxylin and eosin and terminal dUTP transferase nick end labelling.Results Opa3+/+ and Opa3+/‐ mice showed normal visual acuity by tracking a 2° grating. However, Opa3‐/‐ mice displayed no optomotor response at any grating frequency. Despite this, their pupil response was little affected. Pupil response/intensity curves of Opa3‐/‐ and Opa3+/+ mice diverged somewhat at lower intensities although they only differed significantly at two irradiance levels. At 50% constriction Opa3‐/‐ mice were only 0.61 log units less sensitive than wildtypes. Histology showed panretinal degeneration in adult Opa3‐/‐ mice and TUNEL revealed increased cell death in postnatal and adult Opa3‐/‐ retinae.Conclusion The Opa3‐/‐ mouse is a useful model of the human disease. Retinal atrophy in Opa3‐/‐ animals is associated with widespread retinal thinning. However, dissociation between visual perception and pupillary function implies that the intrinsically photosensitive retinal ganglion cells (ipRGCs) subserving pupillary function may be less susceptible to damage by mutations of Opa3 than the retinogeniculate fibres underlying visual perception.