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The light-sensing apparatus of the eye is found within the rods and cones - two types of specialized cells located in the
posterior of the retina. Of the two types of receptors, rod cells exhibit greater light sensitivity (lower threshold) and a
slower reaction time. Cone cells, on the other hand, respond rapidly, and provide greater discrimination of temporal,
spatial, and spectral detail. The light signal captured by photoreceptor cells triggers a cascade of chemical reactions,
called phototransduction, that ultimately generates a neuronal signal.
Like the rod cell, cone cell activation involves the photoisomerization of the 11-cis-retinal chromophore bound to an
opsin-like transmembrane protein. In the case of the cone cell, however, there are three variants of the transmembrane
protein. When bound to the chromophore, each of the resulting visual receptor pigments exhibit a characteristic red, blue,
or green absorption maxima which leads ultimately to color vision. Recent work indicates that the differences in absorption
maxima are a function of differences in amino acid sequences within each pigment. Similar analyses of structure, reactivity
and function will have to be performed for all the critical receptors, catalysts (G-proteins, kinases, phosphoesterases,
retinal dehydrogenases), and reaction terminators (arrestins, recoverins, guanylate cyclase activating proteins) within the
cone cells phototransduction cycle.
Light-triggered events initiated in rod and cone outer segments were the subject of numerous investigations during the last
two decades, most notably using molecular approaches and electrophysiological measurements of the isolated retina or
photoreceptor cells. The light events are intimately intertwined with the regeneration reactions that involve two cell
systems. Every photon of light that triggers photoisomerization is counterbalanced by regeneration of rhodopsin with newly
synthesized 11-cis-retinal. Contributions from numerous investigators have provided substantial advances in our fundamental
knowledge of phototransduction and the regeneration of rhodopsin. These have included the identification of
phototransduction and retinoid processing enzymes, cation channels, and retinoid-binding proteins in the retina-RPE system,
and determination of the mechanisms of action of these proteins. Furthermore, within the past decade there has been
substantial new information regarding the links between specific retinal diseases and identified abnormalities of the
retinoid cycle.
Many unresolved issues relevant to phototransduction, light- and dark-adaptation, and the chemical processing of retinoid
cycle intermediates remain unanswered, including the enzymology of the retinoid cycle, the mechanisms by which these
intermediates diffuse within and between the photoreceptors and the RPE, and the dependence of phototransduction reactions
on the operation of the cycle. These important questions pose exciting challenges for future research on the visual cycle,
and are certain to continue as the subject of intense interest for my laboratory.
Knowledge about phototransduction in the retina, a system with great experimental advantages, will improve further
understanding of similar events in hormonal signaling, cellular communication and immune regulation, and provide baseline
information for further studies of retinal disease processes.
Rhodopsin Dimer (upper right)
GCAP (bottom left)
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