Rod photoreceptors approach the ultimate in sensitivity to light but are also capable of adjusting that sensitivity over a wide range of ambient lighting conditions. This process of light adaptation is important because it extends the dynamic range over which rods are capable of encoding visual information. The goal of these studies is to understand the molecular bases for the changes in rod photoreceptor sensitivity that take place in the presence of steady illumination. Light adaptation is known to involve Ca+2 feedback onto the phototransduction cascade accelerating rhodopsin shutoff, increasing cGMP production and opening ion channels at lower levels of cGMP. At least some of these feedback mechanisms operate rapidly and cause the response to steps of light to partially recover or droop. This droop is essentially complete in a few seconds and helps to keep the rod from saturating so that it can continue to signal changes in light intensity. From suction electrode recordings on single rods of amphibians, we have obtained evidence that there is a component of light adaptation that operates on a slower time scale. The time course and magnitude of desensitization of the slow component will be measured. The dependency of the slow component upon Ca+2 feedback will be determined. Then three putative mechanisms will be tested: transducin's lifetime shortens as cGMP dissociates from noncatalytic sites on PDE, transducin availability decreases because phosducin prevents its recycling, the cGMP-gated channel opens at lower concentrations of cGMP due to a change in its apparent affinity for cGMP. The three mechanisms are not mutually exclusive. Interestingly, light adaptation in amphibian rods far surpasses that in mammalian rods. Two hypotheses will be explored. First, biochemical methods will be used to test whether the decrease in transducin's lifetime during light adaptation in amphibian rods due to the dissociation of cGMP from noncatalytic sites on phosphodiesterase fails to occur in mammalian rods, because cGMP binds much more tightly to these sites on mammalian PDE. Second, rare, aberrant, prolonged single photon responses occur in mammalian rods, but have not been seen in amphibian rods. The cumulative effects of aberrant responses during exposures to steps of light may drive mammalian rods into saturation prematurely. Suction electrode recording will be used to assess the impact of aberrant responses on light adaptation in wild type mouse rods and in rods where the frequency of aberrant responses is higher than normal. Aberrant responses occur with higher frequency in some human retinal diseases and severely limit the intensity range of scotopic vision.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Mariani, Andrew P
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts Eye and Ear Infirmary
United States
Zip Code
Isayama, Tomoki; McCabe England, S L; Crouch, R K et al. (2009) Beta-ionone activates and bleaches visual pigment in salamander photoreceptors. Vis Neurosci 26:267-74
Liu, Xiaoqing; Pawlyk, Basil S; Adamian, Michael et al. (2009) Increased light exposure alleviates one form of photoreceptor degeneration marked by elevated calcium in the dark. PLoS One 4:e8438
Yang, Jun; Pawlyk, Basil; Wen, Xiao-Hong et al. (2007) Mpp4 is required for proper localization of plasma membrane calcium ATPases and maintenance of calcium homeostasis at the rod photoreceptor synaptic terminals. Hum Mol Genet 16:1017-29
He, Quanhua; Alexeev, Dmitriy; Estevez, Maureen E et al. (2006) Cyclic nucleotide-gated ion channels in rod photoreceptors are protected from retinoid inhibition. J Gen Physiol 128:473-85
Makino, Clint L; Wen, Xiao-Hong; Michaud, Norman et al. (2006) Effects of low AIPL1 expression on phototransduction in rods. Invest Ophthalmol Vis Sci 47:2185-94
Makino, Clint L; Dodd, R L; Chen, J et al. (2004) Recoverin regulates light-dependent phosphodiesterase activity in retinal rods. J Gen Physiol 123:729-41
Olshevskaya, Elena V; Calvert, Peter D; Woodruff, Michael L et al. (2004) The Y99C mutation in guanylyl cyclase-activating protein 1 increases intracellular Ca2+ and causes photoreceptor degeneration in transgenic mice. J Neurosci 24:6078-85
Calvert, Peter D; Govardovskii, Victor I; Arshavsky, Vadim Y et al. (2002) Two temporal phases of light adaptation in retinal rods. J Gen Physiol 119:129-45
Calvert, Peter D; Makino, Clint L (2002) The time course of light adaptation in vertebrate retinal rods. Adv Exp Med Biol 514:37-60