Deciphering primate retinal aging at single-cell resolution
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Protein & Cell
LETTER
Dear Editor, The retina is a light-sensitive highly-organized tissue, which is vulnerable to aging and age-related retinal diseases. Specifically, progressive retinal degeneration leads to visual function deterioration and vision impairment in the elderly (Lin et al., 2016). In diseases such as age-related macular degeneration (AMD), retinitis pigmentosa (RP) and diabetic retinopathy (DR), pathological process lacking effective treatments profoundly and negatively impact on the quality of life in the elderly (Lin et al., 2016; Chen et al., 2019). Thus, an in-depth molecular assessment of the mechanisms driving retinal aging is of urgent scientific and medical importance. The retina comprises a layered structure with neural retina and a layer of retinal pigment epithelium (RPE). The neural retina consists of elaborate neuronal circuitry for the detection of visual information whereas the RPE and adjacent choroid layer (a vascularized and pigmented connective tissue) provide nutrition and physical and metabolic support. The neural retina layer mainly contains three demarcated cellular populations, photoreceptors (PRs), interneurons and retinal ganglion cells (RGCs). PRs, including rod and cone photoreceptors (Rod and Cone for abbreviation), convert light into an electrical signal and then transfer it to interneurons (bipolar cells, for instance). Interneurons then transmit the signal to RGCs, whose axons coalesce into the optic nerve projecting to the visual cortex. In addition, the neural retina layer contains many other cells, for example, Müller glial cells (Müller), which serve as supporting cells for the neurons. With aging, the retina undergoes a series of alterations, including physiological, structural and functional alterations, reflected as morphologic changes and/or loss of PRs and RGCs, decreased Rod- and Cone-mediated responses to light, impaired RPE function, and immune dysregulation (Lin et al., 2016; Chen et al., 2019). Due to ethical constraints and limited access to diseasefree human retina tissues, in-depth studies of human retinal degeneration are not practically feasible. As a result, nonhuman primates (NHPs), including crab-eating macaques (Macaca fascicularis), have become a widely used primate model in retinal studies, as they share very similar genetic and physiological characteristics with humans (Li et al.,
© The Author(s) 2020
2020; Wang et al., 2020; Zhang et al., 2020). Most of the retinal cell types have been identified primarily by morphological criteria, which lacks the molecular resolution necessary for dissecting aging-related changes in the primate. With the advent of single-cell RNA sequencing (scRNA-seq) technologies, in-depth molecular surveys of cellular taxonomy and aging mechanism of primate ovary, aorta and pancreatic islet have been achieved (Li et al., 2020; Wang et al., 2020; Zhang et al., 2020). However, the effects of aging on retinal cell types including those present in neural retina and RPE, as well as cell types in choroid layer remain largely
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