Mammals see when light reflected from an object strikes a visual pigment in the eye, which sends a signal to the brain and simultaneously consumes the light-sensitive pigment in retinal photoreceptor cells. In theory, this could present a problem because mammals cannot see if the light-sensitive pigments are depleted. But now UCLA researchers have learned why that never happens. They observed that in bright light mammals rapidly recycle spent pigments, ensuring that photoreceptors retain levels of light-sensitive pigments sufficient for uninterrupted sight.
When stimulated, the light-sensitive pigment in the retina — called 11-cis retinal — oxidizes to a light-insensitive form called all-trans. Nobel Prize-winning work conducted 50 years ago demonstrated that mammals use an enzyme pathway called the visual cycle to convert all-trans back to light-sensitive 11-cis retinal. When scientists learned that multi-step enzymatic reactions like this often work slowly, it presented a mystery. How could the classic pathway replenish the 11-cis retinal fast enough in bright light, which oxidizes the light-sensitive pigment more quickly than dim light conditions?
The team performed a biochemical analysis using cow and mouse retinas. First, the researchers verified that light energy can convert N-ret-PE to 11-cis retinal in a test tube in the absence of visual cycle enzymes. Next they confirmed that pigments regenerate like this in retinas of living mice. Finally, they depleted light-sensitive 11-cis retinal from mouse retinas, allowed pigment to regenerate over time with and without light, and then calculated whether newly-regenerated pigment came from the visual cycle or N-ret-PE. In some conditions, almost half of the 11-cis retinal came from N-ret-PE, confirming that the discovery is highly relevant, not just something that occurs in rare circumstances.
Regeneration of visual pigments by light has never been reported in animals. This discovery answers the question of how animals (including humans) can see over long daylight periods, where demand for 11-cis retinal exceeds the ability of enzymatic reactions to resupply it. It is also an example of a metabolic process in animals “powered” by solar energy. It was previously thought that only plants could capture the energy of sunlight to fuel chemical reactions.
All of the study’s authors are affiliated with the Jules Stein Eye Institute at UCLA. The first author is Dr. Joanna Kaylor; the senior author is Dr. Gabriel Travis, who also is part of the department of biological chemistry. Additional co-authors include Dr. Gordon Fain, Tongzhou Xu, Norianne Ingram, Avian Tsan, and Hayk Hakobyan.
Travis will present the study’s findings at the 50th anniversary celebration seminar for the Jules Stein Eye Institute at UCLA on June 9.