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

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.

Research progress on the role of Müller glial cells in retinal nerve injury / 国际眼科杂志(Guoji Yanke Zazhi)

Müller glial cells(MGCs)are the major type of glial cells in the retina which radiating across the entire retina. MGCs make a close contact with retinal neurons, interact, and contribute to retinal homeostasis. After retinal nerve injury, MGCs respond to retinal injury in a variety of regulatory ways to protect the inner retinal environment changes and damage, producing retinal neuroprotective effects, such as regulating neurotransmitters release, releasing neuroprotective factors and antioxidant factors and reprogramming for endogenous repair. However, persistent pathological stimulation in retina can also exacerbate MGCs' proliferation which participate in neuronal dysfunction or loss. Therefore, a proper understanding of the response of MGCs to pathological stimuli and their protective and damaging effects will have a great impact on revealing mechanisms of retinal nerve damage disease and guiding the treatment of the disease. This article reviews the role of MGCs in retinal nerve injury and repair and provides new strategies for retinal neuroprotection.