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The Journal of Neuroscience, April 8, 2009, 29(14):4616-4621; doi:10.1523/JNEUROSCI.0063-09.2009

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Behavioral/Systems/Cognitive
Normal Cone Function Requires the Interphotoreceptor Retinoid Binding Protein

Ryan O. Parker,¹ Jie Fan,² John M. Nickerson,³ Gregory I. Liou,⁴ and Rosalie K. Crouch²

Departments of ¹Neurosciences and ²Ophthalmology, Medical University of South Carolina, Charleston, South Carolina 29403, ³Department of Ophthalmology, Emory University, Atlanta, Georgia 30322, and ⁴Department of Ophthalmology, Medical College of Georgia, Augusta, Georgia 30912

Correspondence should be addressed to Ryan O. Parker, Storm Eye Institute, Medical University of South Carolina, 167 Ashley Avenue, Charleston, SC 29403-5836. Email: parkerry{at}musc.edu

11-cis-retinal is the light-sensitive component in rod and cone photoreceptors, and its isomerization to all-trans retinal in the presence of light initiates the visual response. For photoreceptors to function normally, all-trans retinal must be converted back into 11-cis-retinal through a series of enzymatic steps known as the visual cycle. The interphotoreceptor retinoid-binding protein (IRBP) is a proposed retinoid transporter in the visual cycle, but rods in Irbp^–/– mice have a normal visual cycle. While rods are primarily responsible for dim light vision, the ability of cones to function in constant light is essential to human vision and may be facilitated by cone-specific visual cycle pathways. We analyzed the cones in Irbp^–/– mice to determine whether IRBP has a cone-specific visual cycle function. Cone electroretinogram (ERG) responses were reduced in Irbp^–/– mice, but similar responses from Irbp^–/– mice at all ages suggest that degeneration does not underlie cone dysfunction. Furthermore, cone densities and opsin levels in Irbp^–/– mice were similar to C57BL/6 (wild-type) mice, and both cone opsins were properly localized to the cone outer segments. To test for retinoid deficiency in Irbp^–/– mice, ERGs were analyzed before and after intraperitoneal injections of 9-cis-retinal. Treatment with 9-cis-retinal produced a significant recovery of the cone response in Irbp^–/– mice and shows that retinoid deficiency underlies cone dysfunction. These data indicate that IRBP is essential to normal cone function and demonstrate that differences exist in the visual cycle of rods and cones.

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Received Jan. 6, 2009; revised Feb. 5, 2009; accepted March 7, 2009.

Correspondence should be addressed to Ryan O. Parker, Storm Eye Institute, Medical University of South Carolina, 167 Ashley Avenue, Charleston, SC 29403-5836. Email: parkerry{at}musc.edu

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