Apolipoprotein D (APOD) is an atypical apolipoprotein with unknown significance for retinal structure and function. Conversely, apolipoprotein E (APOE) is a typical apolipoprotein with established roles in retinal cholesterol transport. Herein, we immunolocalized APOD to the photoreceptor inner segments and conducted ophthalmic characterizations of ApoD-/- and ApoD-/-ApoE-/- mice. ApoD-/- mice had normal levels of retinal sterols but changes in the chorioretinal blood vessels and impaired retinal function. The whole-body glucose disposal was impaired in this genotype but the retinal glucose metabolism was unchanged. ApoD-/-ApoE-/- mice had altered sterol profile in the retina but apparently normal chorioretinal vasculature and function. The whole-body glucose disposal and retinal glucose utilization were enhanced in this genotype. OB-Rb, both leptin and APOD receptor, was found to be expressed in the photoreceptor inner segments and was at increased abundance in the ApoD-/- and ApoD-/-ApoE-/- retinas. Retinal levels of Glut4 and Cd36, the glucose transporter and scavenger receptor, respectively, were increased as well, thus linking APOD to retinal glucose and fatty acid metabolism and suggesting the APOD-OB-Rb-GLUT4/CD36 axis. In vivo isotopic labeling, transmission electron microscopy, and retinal proteomics provided additional insights into the mechanism underlying the retinal phenotypes of ApoD-/- and ApoD-/-ApoE-/- mice. Collectively, our data suggest that the APOD roles in the retina are context specific and could determine retinal glucose fluxes into different pathways. APOD and APOE do not play redundant, complementary or opposing roles in the retina, rather their interplay is more complex and reflects retinal responses elicited by lack of these apolipoproteins.

中文翻译：

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对 ApoD-/- 和 ApoD-/-ApoE-/- 小鼠的研究揭示了 APOD 对视网膜代谢、功能和脉络膜视网膜血管状态的意义。

载脂蛋白 D (APOD) 是一种非典型载脂蛋白，对视网膜结构和功能的意义未知。相反，载脂蛋白 E (APOE) 是一种典型的载脂蛋白，在视网膜胆固醇转运中具有确定的作用。在这里，我们将 APOD 免疫定位到感光器内段，并对 ApoD-/- 和 ApoD-/-ApoE-/- 小鼠进行眼科表征。ApoD-/- 小鼠的视网膜甾醇水平正常，但脉络膜视网膜血管发生变化，视网膜功能受损。该基因型的全身葡萄糖处理受损，但视网膜葡萄糖代谢没有变化。ApoD-/-ApoE-/- 小鼠视网膜中的甾醇分布发生改变，但脉络膜视网膜脉管系统和功能明显正常。该基因型的全身葡萄糖处理和视网膜葡萄糖利用增强。OB-Rb, 瘦素和 APOD 受体都被发现在感光器内段中表达，并且在 ApoD-/- 和 ApoD-/-ApoE-/- 视网膜中的丰度增加。Glut4 和 Cd36（葡萄糖转运蛋白和清道夫受体）的视网膜水平也分别增加，从而将 APOD 与视网膜葡萄糖和脂肪酸代谢联系起来，并表明 APOD-OB-Rb-GLUT4/CD36 轴。体内同位素标记、透射电子显微镜和视网膜蛋白质组学为 ApoD-/- 和 ApoD-/-ApoE-/- 小鼠视网膜表型的潜在机制提供了额外的见解。总的来说，我们的数据表明 APOD 在视网膜中的作用是特定于上下文的，可以确定视网膜葡萄糖流入不同的途径。APOD和APOE在视网膜中不扮演冗余、互补或相反的角色，