Exploring the hepatic-ophthalmic axis through immune modulation and cellular dynamics in diabetic retinopathy and non-alcoholic fatty liver disease

Abstract Background Dysfunctions within the liver system are intricately linked to the progression of diabetic retinopathy (DR) and non-alcoholic fatty liver disease (NAFLD). This study leverages systematic analysis to elucidate the complex cross-talk and communication pathways among diverse cell po...

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Main Authors: Shuyan Zhang, Jiajun Wu, Leilei Wang, Cheng Zhang, Yinjian Zhang, Yibin Feng
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Human Genomics
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Online Access:https://doi.org/10.1186/s40246-025-00730-z
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author Shuyan Zhang
Jiajun Wu
Leilei Wang
Cheng Zhang
Yinjian Zhang
Yibin Feng
author_facet Shuyan Zhang
Jiajun Wu
Leilei Wang
Cheng Zhang
Yinjian Zhang
Yibin Feng
author_sort Shuyan Zhang
collection DOAJ
description Abstract Background Dysfunctions within the liver system are intricately linked to the progression of diabetic retinopathy (DR) and non-alcoholic fatty liver disease (NAFLD). This study leverages systematic analysis to elucidate the complex cross-talk and communication pathways among diverse cell populations implicated in the pathogenesis of DR and NAFLD. Methods Single-cell RNA sequencing data for proliferative diabetic retinopathy (PDR) and NAFLD were retrieved from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was conducted and followed by pseudo-time analysis to delineate dynamic changes in core cells and differentially expressed genes (DEGs). CellChat was employed to predict intercellular communication and signaling pathways. Additionally, gene set enrichment and variation analyses (GSEA and GSVA) were performed to uncover key functional enrichments. Results Our comparative analysis of the two datasets focused on T cells, macrophages and endothelial cells, revealing SYNE2 as a notable DEG. Notably, common genes including PYHIN1, SLC38A1, ETS1 (T cells), PPFIBP1, LIFR, HSPG2 (endothelial cells), and MSR1 (macrophages), emerged among the top 50 DEGs across these cell types. The CD45 signaling pathway was pivotal for T cells and macrophages, exerting profound effects on other cells in both PDR and NAFLD. Moreover, GSEA and GSVA underscored their involvement in cellular communication, immune modulation, energy metabolism, mitotic processes. Conclusion The comprehensive investigation of T cells, macrophages, endothelial cells, and the CD45 signaling pathway advances our understanding of the intricate biological processes underpinning DR and NAFLD. This research underscores the imperative of exploring immune-related cell interactions, shedding light on novel therapeutic avenues in these disease contexts.
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spelling doaj-art-0d5720f7cd6c4e77997869cf90d35d752025-08-20T02:01:38ZengBMCHuman Genomics1479-73642025-02-0119111610.1186/s40246-025-00730-zExploring the hepatic-ophthalmic axis through immune modulation and cellular dynamics in diabetic retinopathy and non-alcoholic fatty liver diseaseShuyan Zhang0Jiajun Wu1Leilei Wang2Cheng Zhang3Yinjian Zhang4Yibin Feng5Department of Ophthalmology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Ophthalmology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineDepartment of Ophthalmology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineSchool of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongDepartment of Ophthalmology, Longhua Hospital, Shanghai University of Traditional Chinese MedicineSchool of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong KongAbstract Background Dysfunctions within the liver system are intricately linked to the progression of diabetic retinopathy (DR) and non-alcoholic fatty liver disease (NAFLD). This study leverages systematic analysis to elucidate the complex cross-talk and communication pathways among diverse cell populations implicated in the pathogenesis of DR and NAFLD. Methods Single-cell RNA sequencing data for proliferative diabetic retinopathy (PDR) and NAFLD were retrieved from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was conducted and followed by pseudo-time analysis to delineate dynamic changes in core cells and differentially expressed genes (DEGs). CellChat was employed to predict intercellular communication and signaling pathways. Additionally, gene set enrichment and variation analyses (GSEA and GSVA) were performed to uncover key functional enrichments. Results Our comparative analysis of the two datasets focused on T cells, macrophages and endothelial cells, revealing SYNE2 as a notable DEG. Notably, common genes including PYHIN1, SLC38A1, ETS1 (T cells), PPFIBP1, LIFR, HSPG2 (endothelial cells), and MSR1 (macrophages), emerged among the top 50 DEGs across these cell types. The CD45 signaling pathway was pivotal for T cells and macrophages, exerting profound effects on other cells in both PDR and NAFLD. Moreover, GSEA and GSVA underscored their involvement in cellular communication, immune modulation, energy metabolism, mitotic processes. Conclusion The comprehensive investigation of T cells, macrophages, endothelial cells, and the CD45 signaling pathway advances our understanding of the intricate biological processes underpinning DR and NAFLD. This research underscores the imperative of exploring immune-related cell interactions, shedding light on novel therapeutic avenues in these disease contexts.https://doi.org/10.1186/s40246-025-00730-zDiabetic retinopathyNon-alcoholic fatty liver diseaseCell-cell communicationSingle-cell RNA sequencingSYNE2
spellingShingle Shuyan Zhang
Jiajun Wu
Leilei Wang
Cheng Zhang
Yinjian Zhang
Yibin Feng
Exploring the hepatic-ophthalmic axis through immune modulation and cellular dynamics in diabetic retinopathy and non-alcoholic fatty liver disease
Human Genomics
Diabetic retinopathy
Non-alcoholic fatty liver disease
Cell-cell communication
Single-cell RNA sequencing
SYNE2
title Exploring the hepatic-ophthalmic axis through immune modulation and cellular dynamics in diabetic retinopathy and non-alcoholic fatty liver disease
title_full Exploring the hepatic-ophthalmic axis through immune modulation and cellular dynamics in diabetic retinopathy and non-alcoholic fatty liver disease
title_fullStr Exploring the hepatic-ophthalmic axis through immune modulation and cellular dynamics in diabetic retinopathy and non-alcoholic fatty liver disease
title_full_unstemmed Exploring the hepatic-ophthalmic axis through immune modulation and cellular dynamics in diabetic retinopathy and non-alcoholic fatty liver disease
title_short Exploring the hepatic-ophthalmic axis through immune modulation and cellular dynamics in diabetic retinopathy and non-alcoholic fatty liver disease
title_sort exploring the hepatic ophthalmic axis through immune modulation and cellular dynamics in diabetic retinopathy and non alcoholic fatty liver disease
topic Diabetic retinopathy
Non-alcoholic fatty liver disease
Cell-cell communication
Single-cell RNA sequencing
SYNE2
url https://doi.org/10.1186/s40246-025-00730-z
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