Retinal Physiology and Computational Modeling
The initial event in vision is the reception of light by cells (photoreceptors) in the back of the eye, the rods (“night” receptors) and cones (“daytime” receptors). Although photoreceptor structure and function has been studied for more than a century, many fundamental details of their structure and function are not yet understood. The process by which photoreceptors convert light energy into electrical signals is called phototransduction, which begins with absorption of photons of light by pigment molecules (rhodopsin) in the receptor. Each activated rhodopsin molecule initiates a cascade of biochemical reactions that lead to an electrical response in the membrane of the cell, and transmission of that signal to the visual centers in the brain.
We are developing models of rod and cone phototransduction by developing mathematical expressions of the underlying biochemical reactions. The models are refined by comparing their performance with the actual responses of photoreceptors. The models can then be used to simulate biochemical experiments and to make predictions that can help guide future physiological and biochemical research.
Some questions addressed are:
- How do photoreceptors adapt and recover sensitivity despite enormous variations in light environments?
- The range of light levels over which photoreceptors must respond — from a new-moon night to a bright day on the ski slopes — is more than 10 billion to one! Without some powerful mechanism for adapting to different levels, the range of light levels over which we could see would be severely limited.
What makes rods and cones so different?
- The rods are much more sensitive than cones, permitting us to see in very low light levels. Cones provide us with fine detail vision, color vision, have a much faster response than rods and can adapt to a much larger range of light levels than rods. Clarification of the structural and biochemical differences between rods and cones that account for their different properties can provide fundamental insights into the nature of phototransduction.
How do retinal diseases affect photoreceptor function on a biochemical level?
- The genetic causes of many retinal diseases affecting photoreceptors are now coming to be understood in great detail. The models we develop can be used to simulate lesions in phototransduction at the molecular level and to test hypotheses about disease mechanisms.
Collaborators: Terry Hegarty, Spero Nicholas, Tsuyoshi Ohyama., Juan Korenbrot, Daniel Tranchina, Paul Liebman, Trevor D. Lamb.