School of Medicine
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.
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