Given the vast amount of information about photoreceptor structure and function, and the underlying biochemistry, the field of retinal physiology is poised for significant advances in the understanding of vertebrate (and, ultimately, human) phototransduction, permitting a tight linkage between macroscopic photoreceptor behavior and underlying molecular mechanisms. Such integration will contribute significantly to a full understanding of the sole input elements of the visual system, the photoreceptors. The overall goal of the application is the development of a full-range, biophysical/biochemical analysis of vertebrate cone phototransduction. This analysis should provide a comprehensive account of the critical features of vertebrate cone responses under both dark-adapted (DA) and light-adapted (LA) conditions. The development of an accurate, full-range model is a challenge because the dynamic range of input to this nonlinear system is vast. The research will focus on the key unresolved issues in cone transduction, which may be grouped into issues relating to mechanisms of photoreceptor activation and inactivation over their full dynamic range, and issues relating to the mechanisms of gain control and LA and effects of LA on the dynamics and sensitivity of cone responses. To ensure maximum accuracy and physiological relevance, the model will be constrained by the current estimates of relevant biochemical pathways and parameters within the biochemical cascade, and will be quantitatively optimized to fit electrophysiological responses of individual cones. In addition, the model will be required to account for critical, qualitative features in a suite of cone responses obtained under a broad range of DA and LA conditions. The data required to evaluate key model predictions will be obtained from single cones from the eyes of bass (Morone saxatilis), with both stimulus and data-acquisition protocols tailored for the planned analyses. A complete account of activation, recovery and LA processes would fully account for both the temporal properties and sensitivity of photoreceptors. These properties completely characterize the photoreceptor signal available to the rest of the visual system. Thus, the project has direct relevance to understanding the role photoreceptors play in shaping the temporal properties and sensitivity of human vision. Moreover, development of a comprehensive, biochemically-based model can provide a powerful tool for evaluating new candidate mechanisms of phototransduction. Similarly, such models allow one to conceptualize and test, noninvasively, putative mechanisms underlying retinal diseases affecting photoreceptor function, and also to identify receptoral immaturities in developing visual systems.
| Hamer, R D; Nicholas, S C; Tranchina, D et al. (2005) Toward a unified model of vertebrate rod phototransduction. Vis Neurosci 22:417-36 |
| Hamer, R D; Nicholas, S C; Tranchina, D et al. (2003) Multiple steps of phosphorylation of activated rhodopsin can account for the reproducibility of vertebrate rod single-photon responses. J Gen Physiol 122:419-44 |
| Hamer, R D (2000) Analysis of Ca++-dependent gain changes in PDE activation in vertebrate rod phototransduction. Mol Vis 6:265-86 |
| Hamer, R D (2000) Computational analysis of vertebrate phototransduction: combined quantitative and qualitative modeling of dark- and light-adapted responses in amphibian rods. Vis Neurosci 17:679-99 |
