Moran Eye Center

Dr. Fu Publishes New Science Regarding Human Red Cone Pigment in Nature Neuroscience

*Fu, Y., Kefalov, V., Luo, D. G., Xie, T., Yau, K.W. Quantal noise from human red cone pigment. (2008) Nature Neuroscience. 11: 565-571.

Dr. Fu describes the power of modern genetics that helped uncover this science:

"Our ability to detect dim lights is limited by noise in photoreceptors. These electrical events, i.e. dark noise, produced in the dark which is indistinguishable from the real signal produced by light especially limit visual sensitivity at low levels of illumination. The question of dark noise in vision has had a long intellectual history from the point of view of psychophysics and system neuroscience. The quantitative agreement between the quantal noise measured from single rods (done in the early and mid- 1980s) and that measured in human psychophysics was considered a breakthrough in the vision field and a wonderful convergence between cell physiology and human psychophysics/system neuroscience, the goal of modern neuroscience after all. On the other hand, the apparent discrepancy between the bottom-up and top-down approaches regarding the quantal noise in cones (1,000-fold higher equivalent dark light in single cones than that measured from psychophysics) has remained a puzzle and setback for many years. The key stumbling block has been the impossible task of measuring quantal noise (spontaneous isomerization) of cone pigment owing to the tiny, irresolvable single-photon responses in native cones. As a way to address this long-standing problem, Dr. Fu and colleagues have successfully expressed human red cone pigment in the rods of mouse, which uses vitamin-A1 pigments like human, so that single spontaneous isomerization events of cone pigment could be observed through the high-amplification rod transduction pathway, especially after genetic removal of a key negative-feedback regulation.

At the same time, the data underscore an important quantitative difference between A1 visual pigments (used by human and other land-based animals) and A2 pigments (used by aquatic species and amphibians). The results provide an answer to another puzzle in vision: Different cone types in lower vertebrates show different sensitivities, but primate red, green, and blue cones all have comparable sensitivities. As such, the paper deals with a phenomenon that is intrinsic to our everyday existence. It also should be of interest to readers in cellular physiology, photochemistry, system neuroscience and psychophysics.

The measurement on the dark noise of human red cone pigment by Dr. Fu and co-workers, which many vision scientists have dreamed for several decades, represents a major breakthrough in this area. The successful story is a manifestation on the power of modern genetics.

Congratulations Dr. FU!