Metabolic Deregulation of the Blood-Outer Retinal Barrier in Retinitis Pigmentosa

Authors

Wei Wang, , University of Louisville Health Sciences Center
Ashwini Kini, University of Louisville Health Sciences Center
Yekai Wang, West Virginia University
Tingting Liu, University of Louisville Health Sciences Center, The Third Affiliated Hospital of Dalian Medical University,
Yao Chen, University of Louisville Health Sciences Center
Eric Vukmanic, University of Louisville Health Sciences Center
Douglas Emery, University of Louisville Health Sciences Center
Yongqing Liu, University of Louisville Health Sciences Center
Xiaoqin Lu, University of Louisville Health Sciences Center
Lei Jin, University of Louisville Health Sciences Center, The Affiliated Hospital of Shandong Traditional Chinese Medicine University
San Joon Lee, niversity of Louisville Health Sciences Center, Kosin University College of Medicine
Patrick Scott, University of Louisville Health Sciences Center
Xiao Liu, University of Louisville Health Sciences Center, Second Xiangya Hospital of Central South University
Kevin Dean, University of Louisville Health Sciences Center
Qingxian Lu, University of Louisville Health Sciences Center
Enzo Fortuny, University of Louisville Health Sciences Center
Robert James, University of Louisville Health Sciences Center
Henry J. Kaplan, University of Louisville Health Sciences Center
Jianhai Du, West Virginia UniversityFollow
Douglas C. Dean, University of Louisville Health Sciences Center

Document Type

Article

Publication Date

2019

College/Unit

School of Medicine

Department/Program/Center

Ophthalmology

Abstract

Retinitis pigmentosa (RP) initiates with diminished rod photoreceptor function, causing peripheral and nighttime vision loss. However, subsequent loss of cone function and high-resolution daylight and color vision is most debilitating. Visual pigment-rich photoreceptor outer segments (OS) undergo phagocytosis by the retinal pigment epithelium (RPE), and the RPE also acts as a blood-outer retinal barrier transporting nutrients, including glucose, to photoreceptors. We provide evidence that contact between externalized phosphatidylserine (PS) on OS tips and apical RPE receptors activates Akt, linking phagocytosis with glucose transport to photoreceptors for new OS synthesis. As abundant mutant rod OS tips shorten in RP, Akt activation is lost, and onset of glucose metabolism in the RPE and diminished glucose transport combine to cause photoreceptor starvation and accompanying retinal metabolome changes. Subretinal injection of OS tip mimetics displaying PS restores Akt activation, glucose transport, and cone function in end-stage RP after rods are lost.

Digital Commons Citation

Wang, Wei; Kini, Ashwini; Wang, Yekai; Liu, Tingting; Chen, Yao; Vukmanic, Eric; Emery, Douglas; Liu, Yongqing; Lu, Xiaoqin; Jin, Lei; Lee, San Joon; Scott, Patrick; Liu, Xiao; Dean, Kevin; Lu, Qingxian; Fortuny, Enzo; James, Robert; Kaplan, Henry J.; Du, Jianhai; and Dean, Douglas C., "Metabolic Deregulation of the Blood-Outer Retinal Barrier in Retinitis Pigmentosa" (2019). Faculty & Staff Scholarship. 1920.
https://researchrepository.wvu.edu/faculty_publications/1920

Source Citation

Wang, W., Kini, A., Wang, Y., Liu, T., Chen, Y., Vukmanic, E., Emery, D., Liu, Y., Lu, X., Jin, L., Lee, S. J., Scott, P., Liu, X., Dean, K., Lu, Q., Fortuny, E., James, R., Kaplan, H. J., Du, J., & Dean, D. C. (2019). Metabolic Deregulation of the Blood-Outer Retinal Barrier in Retinitis Pigmentosa. Cell Reports, 28(5), 1323–1334.e4. https://doi.org/10.1016/j.celrep.2019.06.093

Comments

Cell Reports 28, 1323–1334, July 30, 2019 ª 2019 The Author(s). 1323 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).