Autophagy in glaucoma pathogenesis: Therapeutic potential and future perspectives

Li, Min; Gao, Zhaolin; Zhang, Quanpeng; Luo, Aixiang; Xu, Wei-Ye; Duan, Tian-Qi; Wen, Xu-Peng; Zhang, Ru-Qi; Zeng, Ru; Huang, Jufang

doi:10.3389/fcell.2022.1068213

“…6H-I). Interestingly, autophagy has been found to play a crucial role in glaucoma 57, 58 , which is more prevalent in males than females 59, 60 .…”

Section: Resultsmentioning

confidence: 99%

Integrated multi-omics single cell atlas of the human retina

Li,

Wang,

Ibarra

et al. 2023

Preprint

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Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here, we present an integrated multimodal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 2.4 million cells from 55 donors, including 1.4 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) of transcriptome and chromatin accessibility, unveiling over 110 types. Engaging the retina community, we annotated each cluster, refined the Cell Ontology for the retina, identified distinct marker genes, and characterized cis-regulatory elements and gene regulatory networks (GRNs) for these cell types. Our analysis uncovered intriguing differences in transcriptome, chromatin, and GRNs across cell types. In addition, we modeled changes in gene expression and chromatin openness across gender and age. This integrated atlas also enabled the fine-mapping of GWAS and eQTL variants. Accessible through interactive browsers, this multimodal cross-donor and cross-lab HRCA, can facilitate a better understanding of retinal function and pathology.

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“…In the first case, autophagy leads to irreversible cell atrophy and impaired cell function, ultimately resulting in cell death 35–38 . Numerous studies have provided evidence indicating the crucial role of autophagy in the pathogenesis of glaucoma 39–41 . Dysregulation of autophagy in trabecular meshwork triggers TM cell death and leads to blockage of aqueous humor outflow.…”

Section: Discussionmentioning

confidence: 99%

“…[35][36][37][38] Numerous studies have provided evidence indicating the crucial role of autophagy in the pathogenesis of glaucoma. [39][40][41] Dysregulation of autophagy in trabecular meshwork triggers TM cell death and leads to blockage of aqueous humor outflow. Hence, targeting autophagy may highlight a promising approach for glaucoma treatment.…”

Section: Discussionmentioning

confidence: 99%

DDX58 variant triggers IFN‐β‐induced autophagy in trabecular meshwork and influences intraocular pressure

Huang,

Zhou,

Zhang

et al. 2024

The FASEB Journal

0

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Singleton–Merten syndrome (SMS) is a rare immunogenetic disorder affecting multiple systems, characterized by dental dysplasia, aortic calcification, glaucoma, skeletal abnormalities, and psoriasis. Glaucoma, a key feature of both classical and atypical SMS, remains poorly understood in terms of its molecular mechanism caused by DDX58 mutation. This study presented a novel DDX58 variant (c.1649A>C [p.Asp550Ala]) in a family with childhood glaucoma. Functional analysis showed that DDX58 variant caused an increase in IFN‐stimulated gene expression and high IFN‐β‐based type‐I IFN. As the trabecular meshwork (TM) is responsible for controlling intraocular pressure (IOP), we examine the effect of IFN‐β on TM cells. Our study is the first to demonstrate that IFN‐β significantly reduced TM cell viability and function by activating autophagy. In addition, anterior chamber injection of IFN‐β remarkably increased IOP level in mice, which can be attenuated by treatments with autophagy inhibitor chloroquine. To uncover the specific mechanism underlying IFN‐β‐induced autophagy in TM cells, we performed microarray analysis in IFN‐β‐treated and DDX58 p.Asp550Ala TM cells. It showed that RSAD2 is necessary for IFN‐β‐induced autophagy. Knockdown of RSAD2 by siRNA significantly decreased autophagy flux induced by IFN‐β. Our findings suggest that DDX58 mutation leads to the overproduction of IFN‐β, which elevates IOP by modulating autophagy through RSAD2 in TM cells.

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“…6H-I). Interestingly, autophagy has been found to play a crucial role in glaucoma 57,58 , which is more prevalent in males than females 59,60 .…”

Section: Differential Gene Expression Associated With Age and Sexmentioning

confidence: 99%

Integrated multi-omics single cell atlas of the human retina

Chen,

Li,

Wang

et al. 2023

Preprint

0

View full text Add to dashboard Cite

Single-cell sequencing has revolutionized the scale and resolution of molecular profiling of tissues and organs. Here, we present an integrated multimodal reference atlas of the most accessible portion of the mammalian central nervous system, the retina. We compiled around 2.4 million cells from 55 donors, including 1.4 million unpublished data points, to create a comprehensive human retina cell atlas (HRCA) of transcriptome and chromatin accessibility, unveiling over 110 types. Engaging the retina community, we annotated each cluster, refined the Cell Ontology for the retina, identified distinct marker genes, and characterized cis-regulatory elements and gene regulatory networks (GRNs) for these cell types. Our analysis uncovered intriguing differences in transcriptome, chromatin, and GRNs across cell types. In addition, we modeled changes in gene expression and chromatin openness across gender and age. This integrated atlas also enabled the fine-mapping of GWAS and eQTL variants. Accessible through interactive browsers, this multimodal cross-donor and cross-lab HRCA, can facilitate a better understanding of retinal function and pathology.

show abstract

Autophagy in glaucoma pathogenesis: Therapeutic potential and future perspectives

Cited by 8 publications

References 147 publications

Integrated multi-omics single cell atlas of the human retina

Integrated multi-omics single cell atlas of the human retina

DDX58 variant triggers IFN‐β‐induced autophagy in trabecular meshwork and influences intraocular pressure

Integrated multi-omics single cell atlas of the human retina

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