Abstract
Purpose: :
Wolfram syndrome is a childhood onset rare genetic disease (1/180,000) featuring diabetes mellitus and optic neuropathy unavoidably progressing towards legal blindness before the age of 20. A Wfs1-/- mouse model has been generated (Ishihara et al, 2004), showing pancreatic beta cell atrophy. It is not known whether the mice undergo visual impairment and therefore, visual function and histopathology of Wfs1-/- mice were investigated.
Methods: :
Electroretinogram testing (ERG, retinal function) and visual evoked potentials (VEPs, visual pathway) were performed in Wfs1-/- and Wfs1+/+ mice at 3, 6, 9, 10 and 12 months of age. Fundi were pictured with Micron III apparatus (Phoenix Research Laboratories Inc., Pleasanton,CA). Retinal ganglion cell (RGC) proportion in nerve fiber layer was determined from Brn3a immunolabeling of retinal sections. RGC axonal loss was also quantified by electron microscopy in transversal optic nerve sections.
Results: :
Both a- and b-wave ERG amplitudes were slightly reduced and remained constant through 3 to 12 months. In contrast, VEPs showed progressive decrease of N+P amplitudes in Wfs1-/- by 10, 40 and 50 % at 3, 6 and 9 months, respectively, as compared with controls. Some Wfs1-/- mice showed alterations in the optic disc appearance. RGC proportion and optic nerve axon density in 10 month-old Wfs1-/- mice were slightly decreased, albeit non significantly.
Conclusions: :
Progressive VEPs alteration with minimal cell loss suggests functional alteration of the signal conduction in the optic pathway. Additional functional (optokinetic responses) and immunohistological investigations are underway.
Keywords: neuro-ophthalmology: optic nerve • visual impairment: neuro-ophthalmological disease • inner retina dysfunction: hereditary