In a wide variety of retinal degeneration disease models, the rods and cones die by a special genetically controlled pathway called apoptosis. This form of cell death differs from the more classical form of cell death, termed necrosis because the dying cells do not attract inflammation nor do the cells burst and release their cell contents. Rather, they shrink, fall apart and are removed by their neighbors. We are interested in this process because apoptosis of rods in the human eye, in response to mutations of genes expressed only in rods seems to spread to the neighboring cones leading to blindness. Why should cones die if rods die? Is this invariable or can cones survive in the absence of rods. Some patients with retinitis pigmentosa retain excellent vision indicating that their cones have survived. We now have a model of this experience in one of our frogs. The figures show that the rods die as soon as they begin to express a mutant rab8 protein (rab8-22N).

Thereafter, the retinal cones survive leading to an all-cone retina in a frog that is genetically designed to have a rod-cone retina. These valuable frogs are being studied to determine what factors lead to cone survival. Other transgenic frogs expressing other mutant proteins (mutant rhodopsins, rab8-67L) appear to develop a combined slower rod/cone degeneration which mimics the lesions seen in humans, dogs and cats. We will study the genetic differences in these retinas to assess which genes are protective and which provoke apoptosis.