RHODOPSIN TRANSGENIC PIGS AS A MODEL FOR HUMAN RETINITIS-PIGMENTOSA

PURPOSE. To further characterize the retinas of Pro34Leu rhodopsin tra nsgenic pigs, a model for human retinitis pigmentosa. METHODS. Retinas from normal and transgenic pigs, newborn to 20 months old, were proce ssed for Light and electron microscopic immunocytochemical examination . RESULTS. At birth, rod numbers were normal in the transgenic retinas , but their outer segments were short and disorganized and their inner segments contained stacks of rhodspsin-positive membranes. The newbor n rod synapses lacked synaptic vesicles and ribbons and had numerous r hodopsin-positive, filopodia-like processes that extended past the con e synapses into the outer plexiform layer. Rod cell death was apparent by 2 weeks and was pronounced in the mid periphery and central region s by 6 weeks. Far peripheral rods mere initially better preserved, but by 9 months virtually all rods had degenerated. Cones degenerated mor e slowly than rods, but by 4 weeks the cone synapses were shrunken and some mid peripheral cones had lost their immunoreactivity for phospho diesterase-gamma, arrestin, and recoverin. From 9 months to 20 months, the cone outer segments shortened progressively, and more cones lost immunoreactivity for these proteins. CONCLUSIONS. The rhodopsin transg enic pig retina shares many cytologic features with human retinas with retinitis pigmentosa and provides an opportunity to examine the earli est stages in photoreceptor degeneration, about which little is known in humans. The finding of abnormal rhodopsin localization in newborn r ods is consistent with misrouting of mutant rhodopsin as an early proc ess leading to rod cell death. Novel changes in the photoreceptor syna pses may correlate with early electrophysiological abnormalities in th ese retinas.