Abstract
Human retinal pigment epithelium cells are arranged in a monolayer that plays an important supporting role in the retina. Although the heterogeneity of specific retinal cells has been well studied, the diversity of hRPE cells has not been reported. Here, we performed a single-cell RNA sequencing on 9,302 hRPE cells from three donors and profiled a transcriptome atlas. Our results identified two subpopulations that exhibit substantial differences in gene expression patterns and functions. One of the clusters specifically expressed ID3, a macular retinal pigment epithelium marker. The other cluster highly expressed CRYAB, a peripheral RPE marker. Our results also showed that the genes associated with oxidative stress and endoplasmic reticulum stress were more enriched in the macular RPE. The genes related to light perception, oxidative stress and lipid metabolism were more enriched in the peripheral RPE. Additionally, we provided a map of disease-related genes in the hRPE and highlighted the importance of the macular RPE and peripheral RPE clusters P4 and P6 as potential therapeutic targets for retinal diseases. Our study provides a transcriptional landscape for the human retinal pigment epithelium that is critical to understanding retinal biology and disease.
Highlights
The retina is a complex structure and contains 10 layers of tissue that are responsible for detecting and converting light into neurochemical information that is transmitted to the brain, resulting in vision
In addition to the two expressed genes, we found that CTGF, FST, KCNMA1, and ADIRF were highly expressed in the macular retinal pigment epithelium (RPE), and RARRES2, CRYAB, FBX O 32, and CHCHD10 were expressed in the peripheral RPE (Figure 1D and Supplementary Table S1)
Our results showed that RPE tissues could be categorized into two clusters, one of which is macular RPE highly expressing ID3 and the other is peripheral RPE cluster expressing CRYAB
Summary
The retina is a complex structure and contains 10 layers of tissue that are responsible for detecting and converting light into neurochemical information that is transmitted to the brain, resulting in vision. The central depression of the macula is called the fovea, where the retina is the thinnest and has only two layers of cells: the retinal pigment epithelium (RPE) and cone cells. The visual formation process requires many types of neurons and supporting cell types. Among these neurons and cells, photoreceptor (PR) cells (rods and cones) convert light into an electrical signal that is transferred to interneurons, including horizontal cells (HCs), bipolar cells (BCs), and amacrine cells (ACs). RPE cells, astrocytes, Müller glia and microglial cells mainly support the metabolism of the retina and play an important role in homeostasis of the retina
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