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

• DOI: 10.1016/j.celrep.2019.06.093
• Publication Date: 2019-07-30T13:48:57Z
• Authors: Wei Wang; Ashwini Kini; Yekai Wang; Tingting Liu; Yao Chen; Eric Vukmanic; Douglas Emery; Yongqing Liu; Xiaoqin Lu; Lei Jin; San Joon Lee; Patrick Scott; Xiao Liu; Kevin Dean; Qingxian Lu; Enzo Fortuny; Robert James; Henry J. Kaplan; Jianhai Du; Douglas C. Dean
• Keywords: Photoreceptor cell; Electroretinography

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