Gordon Fain

Gordon Fain

(310) 206-4281

A-222B, Jules Stein Eye Institute
100 Stein Plaza, UCLA
David Geffen School of Medicine
Los Angeles, CA 90095 Jules Stein Eye Institute
100 Stein Plaza, UCLA
David Geffen School of Medicine
Los Angeles, CA 90095

Affiliations

Distinguished Professor Emeritus, Integrative Biology and Physiology
Member, Brain Research Institute, Molecular, Cellular & Integrative Physiology GPB Home Area, Neuroscience GPB Home Area

Research Interests

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.

Biography

A vertebrate photoreceptor uses a G-protein receptor (rhodopsin) and a G-protein cascade to produce the electrical response that signals a change in light intensity. Powerful new techniques have made it possible to understand the working of this cascade in extraordinary detail. The reason for this is that practically every protein involved in the cascade in a photoreceptor, from the pigment molecule rhodopsin to the G-protein and channels, but including also a large number of control proteins, are expressed only in the photoreceptors and nowhere else in the body. This makes it possible with genetic techniques to create mice in which these proteins have been knocked out, over or under expressed, or replaced with proteins of modified structure. We use electrical recording to study the effects of such genetic alterations on the light responses of mouse rods and cones, in order to understand the role of these proteins in the visual cascade. We are especially interested in modulatory enzymes and their function in light and dark adaptation. We also have a long-standing interest in mechanisms of photoreceptor degeneration in genetically inherited disease. 

Publications

A selected list of publications: