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J. R. Davies, R. H. Douglas, V. J. Davies, A. Quantock, M. Votruba; Pupillary and Visual Dysfunction in the Opa3 p.L122P Mutated Mouse. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3598.
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© ARVO (1962-2015); The Authors (2016-present)
Mutations of the OPA3 gene are associated with Type 3-methylglutaconic aciduria and dominant optic atrophy and cataract (ADOAC). Early onset bilateral optic atrophy is a common characteristic of both disorders, where retinal ganglion cells (RGCs) are lost. To investigate the function of the OPA3 protein, we have generated a novel ENU-induced mutant mouse carrying the missense mutation p.L122P in exon 2 of the OPA3 gene. Here, we report pupillary and visual dysfunction.
Optokinetic nystagmus, pupillometry and retinal histology were used to explore the visual function of the Opa3 mouse. The right eyes of 6 week old unanaesthetised dark adapted Opa3-/- (n = 5) and Opa3+/+ (n = 5) animals were tested for pupillary light responsiveness by video pupillometry. They were then observed in the visual tracking drum for a head tracking response to 2°, 4° and 8° gratings. Opa3-/- (n = 3) and Opa3+/+ (n = 3) eyes were later taken for histology. Ten retinal sections around the optic nerve were counted for RGCs and retinal layer thickness was measured.
In the optokinetic drum all Opa3+/+ mice could see the 2° grating. However, Opa3-/- mice showed no head tracking response to any of the gratings, indicating that they are functionally blind. Despite this, the pupil response is little affected. The Opa3-/- only differed from the Opa3+/+ significantly at two irradiance levels, with the difference most apparent at lower levels of illumination. At 50% constriction the Opa3-/- mice were only 0.61 log units less sensitive than their wildtype siblings. Histology revealed a statistically significant loss in the number of RGCs and the retinal layer thicknesses showed a thinning of the RGC, inner plexiform and inner nuclear layers.
The dissociation between visual perception and pupillary function in the opa3 mutant implies that the RGCs subserving the pupillary response are less susceptible to damage by mutations of Opa3 than the retinogeniculate fibres which underlie visual perception.
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