T.M. Redmond

Functional and structural evaluation after AAV.RPE65 gene transfer in the canine model of leber's congenital amaurosis

The Briard dog is affected by an autosomal recessively inherited retinal disease with severe, early-onset visual impairment or blindness. The external structures of the eye appear normal but most affected dogs have a rapid, quivering nystagmus and a wider resting pupillary diameter than normal dogs (Narfstrom et al., 1994). Electroretinography (ERG) is diagnostic in puppies, with non-recordable dark adapted responses and either non-recordable or low amplitude photopic ERG responses. The internal structures of the eye are normal appearing up to several years of age. In older animals changes such as attenuation of retinal vasculature and paling of the tapetal fundus are most often present. In 3-4 year-old affected dogs, yellow specks or spots may also be observed, mainly in the central parts of the fundus, that increase and spread peripherally with age.

In vivo assessment of rodent retinal structure using spectral domain optical coherence tomography.

To determine the potential of a commercially available optical coherence tomography (OCT) device (Spectralis™ HRA + OCT, Heidelberg Engineering) for small animal retinal imaging, we achieved to adapt this third generation OCT system to obtain and quantify high-resolution morphological sections of rodent retina in models with acquired and inherited retinal degenerations. Genetically induced (rd1, rho−/−, RPE65) and acquired retinal degeneration (light damage) was similarly clear as in histology and could be followed in a timeline fashion. We were able to detect and analyze a wide range of retinal pathology in a variety of established animal models used in vision research. As this technique allows longitudinal study designs, it will facilitate characterization of disease dynamics while reducing the numbers of study animals needed. Use of identical outcome measures and even the same diagnostic device in animal and clinical studies bears the potential to streamline translational approaches, e.g., in the assessment of putative therapeutic interventions.