Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling.

Min Wei; Yanping Sun; Shouzhen LI; Yunuo Chen; Longfei LI; Minghao Fang; Ronghua Shi; Dali Tong; Jutao Chen; Yuqian MA; Kun QU; Mei Zhang; Tian Xue

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Single-cell profiling reveals Müller glia coordinate retinal intercellular communication during light/dark adaptation via thyroid hormone signaling.

Author: Min WEI ¹ ; Yanping SUN ¹ ; Shouzhen LI ¹ ; Yunuo CHEN ¹ ; Longfei LI ¹ ; Minghao FANG ¹ ; Ronghua SHI ² ; Dali TONG ¹ ; Jutao CHEN ¹ ; Yuqian MA ¹ ; Kun QU ¹ ; Mei ZHANG ¹ ; Tian XUE ¹
Author Information

1. Division of Life Sciences and Medicine, Department of Ophthalmology, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei 230026, China.
2. Division of Life Sciences and Medicine, School of Life Sciences, University of Science and Technology of China, Hefei 230026, China.
Publication Type:Research Support, Non-U.S. Gov't
Keywords: Müller glial cells; intercellular communication; light/dark adaptation; single cell; thyroid hormone signaling
MeSH: Animals; Mice; Dark Adaptation; Light; Retina; Retinal Cone Photoreceptor Cells/metabolism*; Adaptation, Ocular; Neuroglia/physiology*; Cell Communication; Thyroid Hormones
From: Protein & Cell 2023;14(8):603-617
CountryChina
Language:English
Abstract: Light adaptation enables the vertebrate visual system to operate over a wide range of ambient illumination. Regulation of phototransduction in photoreceptors is considered a major mechanism underlying light adaptation. However, various types of neurons and glial cells exist in the retina, and whether and how all retinal cells interact to adapt to light/dark conditions at the cellular and molecular levels requires systematic investigation. Therefore, we utilized single-cell RNA sequencing to dissect retinal cell-type-specific transcriptomes during light/dark adaptation in mice. The results demonstrated that, in addition to photoreceptors, other retinal cell types also showed dynamic molecular changes and specifically enriched signaling pathways under light/dark adaptation. Importantly, Müller glial cells (MGs) were identified as hub cells for intercellular interactions, displaying complex cell‒cell communication with other retinal cells. Furthermore, light increased the transcription of the deiodinase Dio2 in MGs, which converted thyroxine (T4) to active triiodothyronine (T3). Subsequently, light increased T3 levels and regulated mitochondrial respiration in retinal cells in response to light conditions. As cones specifically express the thyroid hormone receptor Thrb, they responded to the increase in T3 by adjusting light responsiveness. Loss of the expression of Dio2 specifically in MGs decreased the light responsive ability of cones. These results suggest that retinal cells display global transcriptional changes under light/dark adaptation and that MGs coordinate intercellular communication during light/dark adaptation via thyroid hormone signaling.