Journal article
Genetic Associations of Rod- and Cone-Mediated Vision in Aging and Age-Related Macular Degeneration
Investigative ophthalmology & visual science, Vol.66(9), 50
07/01/2025
DOI: 10.1167/iovs.66.9.50
PMCID: PMC12282642
PMID: 40673740
Abstract
To compare genetic associations of rod- and cone-driven vision with those previously defined for delayed rod-mediated dark adaptation (RMDA), a functional risk indicator for incident age-related macular degeneration (AMD).
In adults aged ≥60 years with two normal eyes (per the Age-Related Eye Disease Study 9-step scale) or with AMD in one or both eyes, we measured RMDA at 5° superior retina, photopic vision (acuity, contrast sensitivity, light sensitivity), and mesopic vision (low luminance acuity and deficit). Vision associations of risk-conferring single-nucleotide polymorphisms in CFH and ARMS2 genes were adjusted for age and smoking and stratified for the presence of subretinal drusenoid deposit (SDD).
Of 608 participants, 462 had normal maculas and 146 had AMD. Neither ARMS2 nor CFH was significantly associated with AMD stage. Across all eyes, RMDA worsened significantly in association with ARMS2 (P = 0.0005). Associations were stronger in normal eyes than in AMD (P = 0.0012 vs. 0.0580) and in normal eyes lacking SDD (n = 384, P < 0.0024). Across all eyes, RMDA was significantly associated with CFH (P = 0.0023) but not in normal and AMD eyes separately (P = 0.270 vs. 0.0596). RMDA was significantly associated with the number of risk alleles in normal and AMD eyes (P < 0.0001). Low luminance deficit was associated with gene dose for AMD eyes only (P = 0.477).
Of six vision tests, only RMDA was consistently associated with major risk alleles, including ARMS2 (not CFH) in normal eyes, with or without SDD. RMDA assesses dynamic retinoid resupply from the circulation, perhaps presaging SDD. Results are interpreted considering localization of key proteins in Bruch's membrane.
Details
- Title: Subtitle
- Genetic Associations of Rod- and Cone-Mediated Vision in Aging and Age-Related Macular Degeneration
- Creators
- Christine A Curcio - University of Alabama at BirminghamRobert F Mullins - University of IowaEdwin M Stone - University of IowaLukas Goerdt - University of BonnDeepayan Kar - University of Alabama at BirminghamLiyan Gao - University of Alabama at BirminghamGerald McGwin Jr - University of Alabama at BirminghamCynthia Owsley - University of Alabama at Birmingham
- Resource Type
- Journal article
- Publication Details
- Investigative ophthalmology & visual science, Vol.66(9), 50
- DOI
- 10.1167/iovs.66.9.50
- PMID
- 40673740
- PMCID
- PMC12282642
- NLM abbreviation
- Invest Ophthalmol Vis Sci
- ISSN
- 1552-5783
- eISSN
- 1552-5783
- Publisher
- ASSOC RESEARCH VISION OPHTHALMOLOGY INC; ROCKVILLE
- Grant note
- NIH: R01EY026087 Dorsett Davis Discovery FundAlfreda J. Schueler TrustDeutsche Forschungsgemeinschaft Grant: GO 4009/1-1 National Center for Advanced Translational Sciences of the National Institutes of Health: UL1TR001417 Common Fund of the Office of the Director of the National Institutes of HealthNational Cancer InstituteNational Human Genome Research InstituteNational Heart, Lung, and Blood InstituteNational Institute on Drug AbuseNational Institute of Mental HealthNational Institute of Neurological Disorders and Stroke
Acknowledgments Supported by NIH grants R01AG04212 (C.O.) , R01EY029595 (C.O., C.A.C.) , and R01EY027948 (C.A.C.) ; P30EY03039 (insti-tutional) ; NIH UL1TR003096 (Center for Clinical and Transla-tional Science, University of Alabama at Birmingham) ; Dorsett Davis Discovery Fund (C.O.) and Alfreda J. Schueler Trust (C.O.) ; Deutsche Forschungsgemeinschaft Grant GO 4009/1-1 (L.G.) ; unrestricted funds to the Department of Ophthalmol-ogy and Visual Sciences (University of Alabama at Birming-ham) from Research to Prevent Blindness, Inc., EyeSight Foun-dation of Alabama (University of Alabama at Birmingham) ; NIH grants R01EY026087 (R.F.M., E.M.S.) ; and the National Center for Advanced Translational Sciences of the National Institutes of Health (UL1TR001417; (R.F.M., E.M.S.) . The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health and by the National Cancer Institute; the National Human Genome Research Institute; the National Heart, Lung, and Blood Institute; the National Institute on Drug Abuse; the National Institute of Mental Health; and the National Institute of Neurological Disorders and Stroke.
- Language
- English
- Date published
- 07/01/2025
- Academic Unit
- The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; John and Marcia Carver Nonprofit Genetic Testing Laboratory; Ophthalmology and Visual Sciences
- Record Identifier
- 9984848000802771
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