Our long-term goal is to elucidate the cellular mechanisms of early visual processing in the mammalian retina. Light-evoked signals, noise, and receptive fields will be characterized in single rods and cones. The results will be related quantitatively to human vision and visual limitations. The overall objective is to determine how photoreceptor response characteristics shape our visual experience. This proposal focuses specifically on the manner in which ions, metabolites, and electrical signals pass directly between photoreceptors through gap junctions. We will determine the strength of gap junctional coupling between the different photoreceptor types, the extent to which coupling strength is modulated by light and voltage, and the endogenous retinal factors that mediate the modulation. We will also use gap junction-specific antibodies and pharmacological agents to elucidate the molecular mechanisms that influence coupling strength. It has been proposed that the degeneration of cones in patients with retinitis pigmentosa and macular degeneration is due to the generation of cytotoxic molecules in dying rods that are transferred into cones by way of rod-cone gap junctions. Elucidation of the mechanisms involved in modulation of photoreceptor coupling and the identification of specific exogenous factors that can block of coupling will be useful in developing new therapies for sparing cone vision in patients with retinal degenerations.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Biology and Diseases of the Posterior Eye Study Section (BDPE)
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Greenwell, Thomas
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Li, Peter H; Verweij, Jan; Long, James H et al. (2012) Gap-junctional coupling of mammalian rod photoreceptors and its effect on visual detection. J Neurosci 32:3552-62
Packer, Orin S; Verweij, Jan; Li, Peter H et al. (2010) Blue-yellow opponency in primate S cone photoreceptors. J Neurosci 30:568-72
Hornstein, Eric P; Verweij, Jan; Li, Peter H et al. (2005) Gap-junctional coupling and absolute sensitivity of photoreceptors in macaque retina. J Neurosci 25:11201-9
Hornstein, Eric P; Verweij, Jan; Schnapf, Julie L (2004) Electrical coupling between red and green cones in primate retina. Nat Neurosci 7:745-50
Verweij, Jan; Hornstein, Eric P; Schnapf, Julie L (2003) Surround antagonism in macaque cone photoreceptors. J Neurosci 23:10249-57
Schneeweis, D M; Schnapf, J L (2000) Noise and light adaptation in rods of the macaque monkey. Vis Neurosci 17:659-66
Schneeweis, D M; Schnapf, J L (1999) The photovoltage of macaque cone photoreceptors: adaptation, noise, and kinetics. J Neurosci 19:1203-16
Kraft, T W; Schnapf, J L (1998) Aberrant photon responses in rods of the macaque monkey. Vis Neurosci 15:153-9
Schneeweis, D M; Schnapf, J L (1995) Photovoltage of rods and cones in the macaque retina. Science 268:1053-6
Kraft, T W; Schneeweis, D M; Schnapf, J L (1993) Visual transduction in human rod photoreceptors. J Physiol 464:747-65

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