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. Author manuscript; available in PMC: 2018 Nov 1.
Published in final edited form as: Prog Retin Eye Res. 2017 Nov 22;64:131–156. doi: 10.1016/j.preteyeres.2017.11.002

Fig. 7. Energy-deficient photoreceptors drive angiogenesis.

Fig. 7

(a) Dual shortage of glucose (b, metabolized to pyruvate) and FA uptake reduces acetyl-CoA (c, estimated by measuring acetylcarnitine) and (d) TCA (Krebs) cycle intermediate α-KG in Vldlr−/− retina (LC/MS/MS). Together with oxygen (O2), α-KG is an essential co-activator of propyl-hydroxylase dehydrogenase (PHD) that tags HIF-1α for degradation by proline hydroxylation (hydroxyproline). (e) Levels of hydroxyproline residues in WT and Vldlr−/− retinas measured by LC/MS/MS (n = 15 WT, 12 Vldlr−/− animal retinas, P = 0.0004). (f) Hif1a retinal expression in Vldlr−/− photoreceptor layer (P12 retinal flat mounts, Scale: 100 μm; left: extended focus; middle and right panels: 3D confocal IHC, n = 3) where (g) Vegfa was then also secreted and localized (P16 retinal flat mounts, Scale: 100 μm; left: extended focus; middle and right panels: 3D confocal IHC, n = 3 retinas). (h) Human subjects with AMD, either retinal angiomatous proliferation (RAP, n =3) or choroidal neovascularization (CNV, n = 7) had higher VEGFA vitreous levels by ELISA compared to control subjects without pathologic neovessels (macular hole; n = 8). Results are presented as mean ± SEM. *P < 0.05, **P < 0.01, ***P < 0.001. Figure modified, with permission, from (Joyal et al., 2016).