ArticleMolecular neurodegeneration2025
Genetic context modulates aging and degeneration in the murine retina.
Article in Molecular neurodegeneration, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Association of systemic aging and frailty with retinal alterations: insights from an integrated exposome and metabolome framework.GeroScience · 2026Article
- Genetic context alters central nervous system compartment dependent responses to lipopolysaccharide.bioRxiv : the preprint server for biology · 2026Article
- Neuroinflammation in glaucoma: a myriad of cellular pathways and players.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Age-Related Neurovascular Dysfunction in the Retina and Potential Pathogenic Mechanisms.Investigative ophthalmology & visual science · 2026Review
- Crop-OCT: a Fully Integrated Imageomics Pipeline to Identify Regional and Focal Retinopathy in Murine Models.bioRxiv : the preprint server for biology · 2026Article
- Age-related macular degeneration and cerebral amyloid angiopathy have similar pathologies from cholesterol-APOE-amyloid-β-complement mediated inflammation.Progress in retinal and eye research · 2026Review
- Interpretable Aging Signatures in Human Retinal Cell Types Revealed by Single-Cell RNA Sequencing and Sparse Logistic Regression.Ophthalmology science · 2026Article
- Broad Epigenetic Shifts in the Aging Drosophila Retina Contribute to Its Altered Diurnal Rhythmic Transcriptome.Aging cell · 2026Article
- VG-RETFound: a hybrid retinal AI framework for early vision impairment screening through vessel-graph learning and cross-modal fusion.Frontiers in medicine · 2026Article
- A mouse model for hemoglobin SC disease recapitulates characteristic human pathologies.Blood advances · 2025Article
- WSB.bioRxiv : the preprint server for biology · 2025Article
- Beacon of Hope for Age-Related Retinopathy: Antioxidative Mechanisms and Pre-Clinical Trials of Quercetin Therapy.Antioxidants (Basel, Switzerland) · 2025Review
- Advances in ocular aging: combining deep learning, imaging, and liquid biopsy biomarkers.Frontiers in medicine · 2025Review
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Abstract
backgroundAge is the principal risk factor for neurodegeneration in both the retina and brain. The retina and brain share many biological properties; thus, insights into retinal aging and degeneration may shed light onto similar processes in the brain. Genetic makeup strongly influences susceptibility to age-related retinal disease. However, studies investigating retinal aging have not sufficiently accounted for genetic diversity. Therefore, examining molecular aging in the retina across different genetic backgrounds will enhance our understanding of human-relevant aging and degeneration in both the retina and brain-potentially improving therapeutic approaches to these debilitating conditions.
methodsTranscriptomics and proteomics were employed to elucidate retinal aging signatures in nine genetically diverse mouse strains (C57BL/6J, 129S1/SvlmJ, NZO/HlLtJ, WSB/EiJ, CAST/EiJ, PWK/PhK, NOD/ShiLtJ, A/J, and BALB/cJ) across lifespan. These data predicted human disease-relevant changes in WSB and NZO strains. Accordingly, B6, WSB, and NZO mice were subjected to human-relevant in vivo examinations at 4, 8, 12, and/or 18M, including: slit lamp, fundus imaging, optical coherence tomography, fluorescein angiography, and pattern/full-field electroretinography. Retinal morphology, vascular structure, and cell counts were assessed ex vivo.
resultsWe identified common molecular aging signatures across the nine mouse strains, which included genes associated with photoreceptor function and immune activation. Genetic background strongly modulated these aging signatures. Analysis of cell type-specific marker genes predicted age-related loss of photoreceptors and retinal ganglion cells (RGCs) in WSB and NZO, respectively. Fundus exams revealed retinitis pigmentosa-relevant pigmentary abnormalities in WSB retinas and diabetic retinopathy (DR)-relevant cotton wool spots and exudates in NZO retinas. Profound photoreceptor dysfunction and loss were confirmed in WSB. Molecular analyses indicated changes in photoreceptor-specific proteins prior to loss, suggesting photoreceptor-intrinsic dysfunction in WSB. In addition, age-associated RGC dysfunction, loss, and concomitant microvascular dysfunction were observed in NZO mice. Proteomic analyses revealed an early reduction in protective antioxidant processes, which may underlie increased susceptibility to DR-relevant pathology in NZO.
conclusionsGenetic context is a strong determinant of retinal aging, and our multi-omics resource can aid in understanding age-related diseases of the eye and brain. Our investigations identified and validated WSB and NZO mice as improved preclinical models relevant to common retinal neurodegenerative diseases.
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