Proctor Lecture: Practical application of model of photoexcitationin rod receptors

Trevor Lamb, ScD, FRS, FAA, of the John Curtin School of Medical Research, Australian National University, Canberra, Australia, and Edward Pugh Jr., PhD, from the F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, share the 2006 Proctor Medal and Lecture for the development of a comprehensive model of photoexcitation in rod receptors and its application to the electroretinogram (ERG). This work led to the use of the ERG in the analysis of deficits in a variety of basic and clinical situations.

Their presentation, "Phototransduction, Dark Adaptation, and the Retinoid Cycle of Vision," described the minute workings of the photoreceptor layer and the cascade of events that take place in the retina. The process begins when rhodopsin, a component of the rod cells absorbing light, is located in the outer segment and is a member of a super family of G protein-coupled receptors. The chromophore 11-cis retinal, part of rhodopsin, is attached to lysine 296.

Visual transduction is initiated, according to Dr. Pugh, with absorption of a photon of light, the ultimate activation of phosphodiesterase, the enzyme that synthesizes cyclic CMP, and channel closure leading to the recovery of the dark state of the photoreceptors. The substance that seems to be responsible for the dark adaptation is opsin, which is removed from the photoreceptors.

"The hypothesis is that opsin weakly activates the transduction cascade, and opsin recombining with 11-cis retinal eliminates its activity," Dr. Pugh said.

The molecular model of phototransduction that Drs. Lamb and Pugh formulated allowed them to establish a time course of the events and evaluations of ERGs conformed closely to their predictions.

The fruits of their labor become clinically practical in diseases with slow dark adaptation, such as fundus albipunctatus, vitamin A deficiency, and early age-related maculopathy. In vitamin A deficiency, for example, there is less vitamin A in the circulation and dark adaptation is one-third of normal. In age-related maculopathy, the dark adaptation is about two-thirds of normal and provides a method of early diagnosis.

The Proctor Medal, the highest honor the Association for Research in Vision and Ophthalmology bestows, is presented each year for outstanding research in the basic or clinical sciences as they relate to ophthalmology.