Department of Ophthalmology and Vision Science, University of Arizona, Tucson, AZ, USA.
Department of Physiology, University of Arizona, Tucson, AZ, USA.
Adv Exp Med Biol. 2023;1415:43-47. doi: 10.1007/978-3-031-27681-1_7.
Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the developed world. Caucasians are eightfold more likely to develop AMD than any other race, indicating a racial bias in AMD incidence which is unexplained. We hypothesize that pigmentation of the retinal pigment epithelium (RPE) and choroid protects from AMD and underlies this peculiar racial bias. We investigated GPR143, a receptor in the pigmentation pathway, which is activated by a melanin synthesis by-product, l-dopa. In this model, greater pigmentation leads to greater l-dopa production and, in turn, greater GPR143 signaling. GPR143 activity upregulates PEDF and downregulates both VEGF and exosomes; all of which reduce the angiogenic potential in the retina. Moreover, we demonstrate that GPR143 signaling enhances the digestion of shed photoreceptor outer segments. Together, our data suggests a central role for GPR143 signaling in RPE-photoreceptor interaction which is critical to healthy vision.
年龄相关性黄斑变性（AMD）是发达国家导致不可逆性失明的主要原因。白种人患 AMD 的可能性是其他任何种族的八倍，这表明 AMD 的发病率存在种族差异，但原因尚不清楚。我们假设视网膜色素上皮（RPE）和脉络膜的色素沉着可预防 AMD，并构成这种特殊的种族差异的基础。我们研究了 GPR143，这是色素沉着途径中的一种受体，它可被黑色素合成的副产物 l-多巴激活。在该模型中，更多的色素沉着会导致更多的 l-多巴产生，进而导致更多的 GPR143 信号转导。GPR143 活性上调 PEDF，下调 VEGF 和外泌体；所有这些都降低了视网膜的血管生成潜力。此外，我们证明 GPR143 信号转导增强了脱落的光感受器外节的消化。综上所述，我们的数据表明 GPR143 信号转导在 RPE-光感受器相互作用中起核心作用，这对健康的视力至关重要。
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