Scholar - SciOpen

The diabetic mice underwent an 8-week dietary intervention of ad libitum (AL) and IF diet. Meibomian gland (MG) proliferative potential, apoptosis, and ductal hyperkeratinization were assessed using immunofluorescence. Gene expression levels were evaluated by Western blot. Lipid accumulation was observed via LipidTox staining. Transmission electron microscopy (TEM) examined intracellular lipids and mitochondrial ultrastructure in acinar cells. Lipidomic and transcriptomic analyses compared MG gene expression and lipid profiles between groups.

RESULTS

IF ameliorated diabetes-induced MGD. IF significantly improved diabetic MG proliferation, apoptosis and lipid metabolism imbalance, as well as improved the expression of the genes involved in lipid metabolism. Simultaneously, the results of lipidomics indicated that IF can effectively modify the types and content of lipids, especially ceramides and cholesterol esters. Transcriptomic results suggested that IF effectively ameliorated cell death and modulated ion channels signaling. IF could ameliorate cell death which might be mediated by the calcium ion signaling pathway to mitigate diabetes-induced MGD.

CONCLUSION

These results provide direct evidence for the feasibility of dietary intervention to improve diabetes-induced MGD. IF can alter MG lipid composition and inhibit apoptosis in diabetic condition. The underlying mechanism may be associated with calcium ion signaling pathway.

Open Access Full Length Article Issue

The genomic and epigenomic landscape of iridocorneal endothelial syndrome

Yaoming Liu, Gen Li, Jiaxuan Jiang, Sujie Fan, Lan Lu, Ting Wang, Guigang Li, Wenzong Zhou, Xuequn Liu, Yingjie Li, Hong Sun, Liang Liang, Yuhong Tang, Yang Chen, Jianjun Gu, Fei Li, Xiuli Fang, Tao Sun, Aiguo Lv, Yayi Wang, Peiyuan Wang, Tao Wen, Jiayu Deng, Yuhong Liu, Mingying Lai, Jingni Yu, Danyan Liu, Hua Wang, Meizhu Chen, Li Li, Xiaodan Huang, Jingming Shi, Xu Zhang, Kang Zhang, Lingyi Liang, Xiulan Zhang

Genes & Diseases 2025, 12(3): 101448

Published: 06 November 2024

Abstract

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Iridocorneal endothelial (ICE) syndrome is a rare, irreversibly blinding eye disease with an unknown etiology. Understanding its genomic and epigenomic landscape could aid in developing etiology-based therapies. In this study, we recruited 99 ICE patients and performed whole-genome sequencing (WGS) on 51 and genome-wide DNA methylation profiling on 48 of them. We conducted mutational burden testing on genes and noncoding regulatory regions, comparing the ICE cohort with control groups (9197 East Asians from the gnomAD database and 350 normal Chinese from our in-house cohort). Copy number variation (CNV) analysis and differential methylation of regions were also explored. We identified RP1L1 (27/51, 53%) with a significantly higher coding-altering mutational burden in the ICE cohort (p < 8.3×10⁻⁷), with mutations predominantly at chr8:10467637 (hg19). Additionally, 41 regions with significant CNVs were identified, including two regions at chr19:15783859-15791329 (hg19) and chr3:75786061-75790887 (hg19), showing copy number loss in 39 and 19 patients, respectively. We also identified 2,717 differentially methylated regions (DMRs), with hypomethylation prevalent in ICE syndrome (91.9% of DMRs). Among these, 45 recurrent hypomethylated regions (HMRs) in more than 10% of ICE patients showed differential methylation compared to normal controls. This study presents the first comprehensive genomic and epigenomic characterization of ICE syndrome, offering insights into its underlying etiology.

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