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Lei Jin, Wei Wang, Yongqing Liu, Henry J Kaplan, Douglas C. Dean; Mertk Signaling is Important for Transport of Glucose from the RPE to Photoreceptors. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4011. doi: https://doi.org/.
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Mutations in rod-specific genes cause diminished peripheral and night-time vision in retinitis pigmentosa (RP). Previously, we demonstrated that cones become starved for glucose as RP progresses, and replacement of glucose in the subretinal space temporarily restored cone function in RP. Glucose is transported from the choroid circulation to the RPE, and then to photoreceptors. This starvation coincided with shortening of abundant rod outer segments (OS), leading us to hypothesize that OS contact with the RPE was triggering glucose transport from the RPE to photoreceptors. We further study the signal pathway which leading to the glaucose transportation.
Using mice with a P23H Rho or a Mertk mutation as models of RP, we analyzed immunostaining, fluorescent glucose transport from the RPE to photoreceptors, full field ERG, and cone OS length. WT photoreceptor OS were injected into the subretinal space in P23H Rho and Mertk mutant mice.
We show fluorescent glucose is not transported from the RPE to photoreceptors in RP, and this is due to failure of OS to engage Mertk. This photoreceptor starvation causes loss of OS synthesis and function measured by ERG and OKR. Injection of WT OS into P23H Rho mutant mice restored glucose transport to photoreceptors, OS synthesis and function. But, this injection failed to restore glucose transport and photoreceptors function in Mertk mutants, demonstrating that OS engagement of Mertk on the RPE is required for signaling glucose transport.
OS contact with the RPE triggers glucose transport from the RPE to photoreceptors. As abundant rod OS begin to shorten during RP progression, MerTk signaling is lost and glucose becomes sequestered in the RPE causing photoreceptor starvation and loss of function.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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