Cellular physiology of vertebrate retina Light falling on the retina excites a photopigment (rhodopsin), which then triggers an enzymatic cascade in the rod and cone photoreceptors . This cascade reduces the intracellular cGMP concentration and decreases the conductance of the photoreceptor plasma membrane. We use a variety of techniques, including intracellular and extracellular recording, patch-clamp, and fluorescent dye laser spot Ca2+ measurement, in order to understand how visual transduction is modulated by Ca2+ to produce adaptation to light and to darkness. We are also interested in mechanisms of photoreceptor degeneration during inherited retinal dystrophy in diseases like retinitis pigmentosa and Leber's amaurosis. Our work has shown that continuous activation of the visual cascade is the cause of apoptosis in some of these disorders, and that cell death is probably triggered by a prolonged decrease in Ca2+ concentration. Increases in Ca2+ can also trigger apoptosis--the photoreceptor regulates its Ca2+ concentration within a narrow range and uses a variety of protective mechanisms to prevent damage from constant light. Our studies are helping to define mechanisms of Ca2+ regulation that, for rods and cones, are literally a matter of life or death.