Gordon Fain, PhD

Professor
Departments of Physiological Science and Ophthalmology
University of California Los Angeles
Los Angeles, California
January 29, 2007

Light, Calcium, and the Death of Photoreceptors

Exposure of the photoreceptors of the eye to light can produce retinal degeneration. I will describe early experiments showing that even moderate illumination can do this, provided it is given continuously. Apoptosis is not triggered by the light per se—that is, by local heating or ultraviolet light damage—but rather by continuous activation of the transduction cascade. We know this, since mice lacking the G protein transducin, which is essential for cascade activation, do not show degeneration in continuous light. This same mechanism is responsible for degeneration during vitamin A deprivation: in the absence of vitamin A (and thus 11-cis retinal, the visual chromophore), rhodopsin is noisy and activates the cascade much like constant light. Degeneration during vitamin A deprivation is again blocked in mice lacking the G protein transducin. The mechanism of degeneration is unknown, but recent experiments suggest that continuous activation of the cascade may produce death by decreasing the Ca²⁺ to a very low level and keeping it there for a long period of time. Since low Ca²⁺ can cause degeneration of neurons, it seems likely that a similar mechanism may be responsible for photoreceptor apoptosis. We think this mechanism not only is important for light damage and vitamin A deprivation but possibly represents an important pathway for cell death in inherited retinal disease.

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