Regulations of Retinal Inflammation: Focusing on Müller Glia

Chen, Yingying; Xia, Qinghong; Zeng, Yue; Zhang, Yun; Zhang, Meixia

doi:10.3389/fcell.2022.898652

Cited by 13 publications

(10 citation statements)

References 189 publications

(233 reference statements)

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“…Müller glia regulate retinal homeostasis and contribute to retinal inflammation through cytokine/chemokine signaling and interactions with retinal vasculature and microglia [81]. Their proximity to the retinal vasculature and the blood retinal barrier make them an ideal conduit for signaling between the retina and the immune system during stress, injury, and disease to modulate inflammation [81].…”

Section: Resultsmentioning

confidence: 99%

Latent Epigenetic Programs in Müller Glia Contribute to Stress, Injury, and Disease Response in the Retina

Norrie,

Lupo,

Shirinifard

et al. 2023

Preprint

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Previous studies have demonstrated the dynamic changes in chromatin structure during retinal development that correlate with changes in gene expression. However, a major limitation of those prior studies was the lack of cellular resolution. Here, we integrate single-cell (sc) RNAseq and scATACseq with bulk retinal data sets to identify cell type specific changes in the chromatin structure during development. Although most genes promoter activity is strongly correlated with chromatin accessibility, we discovered several hundred genes that were transcriptionally silent but had accessible chromatin at their promoters. Most of those silent/accessible gene promoters were in the Muller glial cells. The Muller cells are radial glia of the retina and perform a variety of essential functions to maintain retinal homeostasis and respond to stress, injury, or disease. The silent/accessible genes in Muller glia are enriched in pathways related to inflammation, angiogenesis, and other types of cell-cell signaling and were rapidly activated when we tested 15 different physiologically relevant conditions to mimic retinal stress, injury, or disease in human and murine retinae. We refer to these as pliancy genes because they allow the Muller glia to rapidly change their gene expression and cellular state in response to different types of retinal insults. The Muller glial cell pliancy program is established during development, and we demonstrate that pliancy genes are necessary and sufficient for regulating inflammation in the murine retina in vivo. In zebrafish, Muller glia can de-differentiate and form retinal progenitor cells that replace lost neurons. The pro-inflammatory pliancy gene cascade is not activated in zebrafish Muller glia following injury, and we propose a model in which species-specific pliancy programs underly the differential response to retinal damage in species that can regenerate retinal neurons (zebrafish) versus those that cannot (humans and mice).

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Section: Resultsmentioning

confidence: 99%

Latent Epigenetic Programs in Müller Glia Contribute to Stress, Injury, and Disease Response in the Retina

Norrie,

Lupo,

Shirinifard

et al. 2023

Preprint

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show abstract

“…It has also been demonstrated that glial cells are involved in retinal inflammation. Indeed, Müller cells have different receptors for cytokines and release cytokines to regulate inflammation ( 8 ). In physiological conditions, microglial cells maintain the homeostasis of the retina, undertake phagocytosis, clear debris, and control inflammation.…”

Section: Functional Anatomy Of the Retina And Blood–retina Barriermentioning

confidence: 99%

The role of the mTOR pathway in diabetic retinopathy

et al. 2022

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The retina, the part of the eye, translates the light signal into an electric current that can be sent to the brain as visual information. To achieve this, the retina requires fine-tuned vascularization for its energy supply. Diabetic retinopathy (DR) causes alterations in the eye vascularization that reduce the oxygen supply with consequent retinal neurodegeneration. During DR, the mammalian target of rapamycin (mTOR) pathway seems to coordinate retinal neurodegeneration with multiple anabolic and catabolic processes, such as autophagy, oxidative stress, cell death, and the release of pro-inflammatory cytokines, which are closely related to chronic hyperglycemia. This review outlines the normal anatomy of the retina and how hyperglycemia can be involved in the neurodegeneration underlying this disease through over activation or inhibition of the mTOR pathway.

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“…Astrocytes are closely related to angiogenesis and play an important role in neurovascular homeostasis. The GFAP has been found to be useful in assessing astrocyte activation levels in previous studies [ 91 ]. It was found that LBPs can protect neurons and blood vessels in acute/chronic ocular hypertension animal models.…”

Section: Lbps and Vascular Retinopathymentioning

confidence: 99%

Effects of Lycium barbarum L. Polysaccharides on Vascular Retinopathy: An Insight Review

Yang

Zhao

et al. 2022

Molecules

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Vascular retinopathy is a pathological change in the retina caused by ocular or systemic vascular diseases that can lead to blurred vision and the risk of blindness. Lycium barbarum polysaccharides (LBPs) are extracted from the fruit of traditional Chinese medicine, L. barbarum. They have strong biological activities, including immune regulation, antioxidation, and neuroprotection, and have been shown to improve vision in numerous studies. At present, there is no systematic literature review of LBPs on vascular retinal prevention and treatment. We review the structural characterization and extraction methods of LBPs, focus on the mechanism and pharmacokinetics of LBPs in improving vascular retinopathy, and discuss the future clinical application and lack of work. LBPs are involved in the regulation of VEGF, Rho/ROCK, PI3K/Akt/mTOR, Nrf2/HO-1, AGEs/RAGE signaling pathways, which can alleviate the occurrence and development of vascular retinal diseases in an inflammatory response, oxidative stress, apoptosis, autophagy, and neuroprotection. LBPs are mainly absorbed by the small intestine and stomach and excreted through urine and feces. Their low bioavailability in vivo has led to the development of novel dosage forms, including multicompartment delivery systems and scaffolds. Data from the literature confirm the medicinal potential of LBPs as a new direction for the prevention and complementary treatment of vascular retinopathy.

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Regulations of Retinal Inflammation: Focusing on Müller Glia

Cited by 13 publications

References 189 publications

Latent Epigenetic Programs in Müller Glia Contribute to Stress, Injury, and Disease Response in the Retina

Latent Epigenetic Programs in Müller Glia Contribute to Stress, Injury, and Disease Response in the Retina

The role of the mTOR pathway in diabetic retinopathy

Effects of Lycium barbarum L. Polysaccharides on Vascular Retinopathy: An Insight Review

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