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Wei Wang, Henry J Kaplan, Douglas C Dean; Contact of Rod Outer Segment Tips with the RPE Triggers Glucose Transport From the RPE to Cone Photoreceptors for OS Synthesis and Function. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3028. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Retinitis Pigmentosa (RP) is the most frequent cause of hereditary visual loss in adults. Mutations most frequently target rod photoreceptors and rod loss results in nyctalopia and a constricted visual field. But,the major visual disability in RP results from subsequent cone photoreceptor dysfunction, leading to diminished high resolution central vision that is required for tasks such as reading and facial recognition. Previously, we demonstrated that transplanted rod precursors could restore host cone function. We linked rod mutation to a failure to transport glucose from the RPE to cone photoreceptors, and provided evidence that directly injecting glucose into the subretinal space could bypass this defect and restore cone OS synthesis and function. Unraveling the mechanism through which rods are required for transport of glucose to cones might reveal a pathway to preserve/restore central cone vision in RP patients with rod mutations.
Using both pig and mouse models of RP carrying a P23H Rho mutation model of RP, we injected purified OS tips from WT animals or glucose into the subretinal space of animals where cone OS synthesis and function was diminished. Then we analyzed fluorescent glucose transport, full field ERG, multifocal ERG, and cone OS length.
We provide evidence RPE contact with long rod OS tips triggers release of glucose from the RPE into the subretinal space, where it is taken up by cones for use in new OS synthesis, and thus, function. As OS formation diminishes in mutant rods in RP, glucose is no longer transported from the RPE to cones, leading to diminished cone OS synthesis and function.
Injection of WT OS tips to trigger glucose release from the RPE or direct injection of glucose into the subretinal space can bypass the glucose transport defect to cones, and thereby restore cone OS synthesis and function in RP models.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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