Evidence mapPaperPMID 40411685Full record

ArticleMolecular neurobiology2025

Peripheral Choroid/RPE/Sclera as a Shared Pathogenic Hub: Multi-Tissue Transcriptomic Profiling Identifies Common Differentially Expressed Genes in Age-Related Macular Degeneration and Alzheimer's Disease.

Manjuan Peng, Qi Zeng, Wei Zheng, Xiaobo Xia

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Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 authors.

Manjuan Peng *Eye Center of Xiangya Hospital, Central South University, Changsha, China.
Qi Zeng *Department of Ophthalmology, Hunan Provincial People's Hospital and The First-Affiliated Hospital of Hunan Normal University, Changsha, China.
Wei ZhengEye Center of Xiangya Hospital, Central South University, Changsha, China.
Xiaobo XiaEye Center of Xiangya Hospital, Central South University, Changsha, China. xbxia21@csu.edu.cn.

Funding

National Key Research and Development Program of China 2020YFC2008205National Natural Science Foundation of China 81974134Research Program of Hunan Provincial Health Commission, China 20200757the Hunan Natural Science Foundation Project, China 2021JJ30397the Hunan Provincial Science and Technology Department Focuses on Research and Development, China 2020SK2119
6 · The paper itself

Abstract

backgroundAge-related macular degeneration (AMD) and Alzheimer's disease (AD), two prevalent neurodegenerative disorders, share overlapping pathophysiological features yet lack cross-disease therapeutic strategies. This study systematically investigates their parallel genes and shared molecular mechanisms to identify potential therapeutic targets for dry AMD, a condition with limited treatment options.

methodsTranscriptomic datasets for AMD (GSE155154) and AD (GSE95587) were retrieved from the GEO database. AMD tissues were stratified into four subgroups: macular retina (MR), macular choroid/RPE/sclera (MCRS), peripheral retina (PR), and peripheral choroid/RPE/sclera (PCRS). Common differentially expressed genes (DEGs) were identified and analyzed via functional enrichment (GO, KEGG), gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) networks. Drug-gene interactions and competing endogenous RNA (ceRNA) networks were constructed to prioritize therapeutic targets. Key hub genes were experimentally validated in a sodium iodate-induced AMD murine model using RT-qPCR.

resultsComparative analysis revealed 89, 56, 4, and 130 common DEGs between AD and MR, MCRS, PR, and PCRS subgroups, respectively. Neuroactive ligand-receptor interactions were prioritized in MR/MCRS-AD analyses, while extracellular matrix organization emerged as the dominant pathway in PCRS-AD comparisons. GSEA identified conserved the TNFα signaling pathway via NF-κB across both diseases. PCRS exhibited consistent expression trends for shared genes and pathways with AD. Computational screening prioritized seven druggable targets (COL1A1, COL1A2, COL3A1, MMP2, MMP9, VCAN, ITGA5) with dual therapeutic potential, along with a reconstructed circRNA (circRNA_002179)-miRNA (miR-124)-mRNA (VCAN) regulatory axis. Experimental validation in a sodium iodate-induced AMD murine model confirmed region-specific dysregulation: hub genes were significantly downregulated in MCRS but upregulated in PCRS.

conclusionsOur study delineates both convergent and divergent molecular landscapes of AMD and AD, with PCRS emerging as a critical locus for shared pathophysiology. These findings bridge a critical gap in understanding AMD-AD comorbidity, offering actionable strategies for targeted drug development.

Indexed as

Alzheimer DiseaseChoroidGene Expression ProfilingMacular DegenerationRetinal Pigment EpitheliumTranscriptomeAnimalsGene Expression RegulationGene OntologyGene Regulatory NetworksHumansMiceProtein Interaction MapsAge-related macular degenerationAlzheimer’s diseaseCOL1 A1Differentially expressed genesExtracellular matrix organizationMMP2MMP9Peripheral choroid/RPE/scleraVCAN

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.