Melanopsin - Discovery

Discovery

Takashi Yoshimura and Shizufumi Ebihara of Nagoya University in Japan discovered in 1994 that although the phase response curves of retinally degenerate CBA/J mice showed smaller delays in the early subjective night than normal CBA/N mice, CBA/J mice could show normal magnitude phase shifts if exposed to sufficiently high intensities of light. From this, they concluded that differences in the shapes of PRCs were due to the differences in photosensitivity of the two mouse strains, and that reduced circadian photosensitivity may be caused by retinal degeneration.

Melanopsin was originally discovered by Ignacio Provencio and his colleagues in 1998, in the specialized light sensitive cells of frog skin. In 1999, Russell G. Foster showed that entrainment of mice to a light-dark cycle was maintained in the absence of rods and cones. Such an observation led him to the conclusion that neither rods nor cones, located in the outer retina, are necessary for circadian entrainment and that a third class of photoreceptor exists in the mammalian eye. In 2000, Provencio determined that melanopsin was expressed only in the inner retina of mammals, including humans, and that it mediated nonvisual photoreceptive tasks.

The first recordings of light responses from melanopsin-containing ganglion cells were obtained by David Berson and colleagues at Brown University. They also showed that these responses persisted when pharmacological agents blocked synaptic communication in the retina, and when single melanopsin-containing ganglion cells were physically isolated from other retinal cells. These findings showed that melanopsin-containing ganglion cells are intrinsically photosensitive, and they were thus named intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). They constitute a third class of photoreceptor cells in the mammalian retina, beside the already known rod and cone photoreceptors.