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Archivos de la Sociedad Española de Oftalmología (English Edition) The potential of DNA methylation as a biomarker for age-related macular degenera...
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Available online 26 March 2026

The potential of DNA methylation as a biomarker for age-related macular degeneration: A systematic review

El potencial de la metilación del ADN como biomarcador de la degeneración macular asociada a la edad: una revisión sistemática
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S. Ghannaia, E. Ribeiroa, B. Pereiraa,b,c, M. Britoa, P. Camachoa,c,
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pedro.camacho@estesl.ipl.pt

Corresponding author.
a H&TRC- Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Lisbon, Portugal
b Retina Institute of Lisbon, Lisbon, Portugal
c iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, NMS, FCM, Universidade NOVA de Lisboa, Lisboa, Portugal
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Abstract

Age-related macular degeneration (AMD) is a multifactorial disease influenced by genetic and environmental factors, yet its pathogenesis remains incompletely understood. DNA methylation, increasingly recognized as a disease indicator, has been linked to AMD and may represent a promising biomarker or therapeutic target. This systematic review, conducted according to PRISMA 2020 guidelines, analyzed 13 studies addressing DNA methylation in AMD populations (2012–2025). Results revealed that 25% reported hypermethylation, 8% hypomethylation, and 41% both patterns, while 15% found no significant differences. Notably, one study described downregulation of DNA methyltransferases in advanced stages compared with early or intermediate AMD. Despite the limited evidence, findings support the relevance of methylation in AMD prognosis and therapy. Further research with robust methodologies is essential to clarify the role of epigenetic mechanisms in disease progression and to explore their potential for guiding targeted therapeutic strategies

Keywords:
Epigenetics
Age-related macular degeneration
DNA methylation
Methylation patterns
Age-related macular degeneration biomarkers
Resumen

La degeneración macular asociada a la edad (DMAE) es una enfermedad multifactorial influenciada por factores genéticos y ambientales, cuya patogénesis aún no se comprende completamente. La metilación del ADN, reconocida como un indicador de enfermedad, se ha vinculado con la DMAE y podría representar un biomarcador o un objetivo terapéutico prometedor. Esta revisión sistemática, realizada según las directrices PRISMA 2020, analizó 13 estudios publicados entre 2012 y 2025. Los resultados mostraron que el 25% informó hipermetilación, el 8% hipometilación y el 41% ambos patrones, mientras que el 15% no observó diferencias significativas. Un estudio destacó la disminución de ADN metiltransferasas en fases avanzadas en comparación con las etapas tempranas o intermedias. Aunque la evidencia sigue siendo limitada, estos hallazgos respaldan la relevancia de la metilación en el pronóstico y el tratamiento de la DMAE. Se requieren investigaciones más sólidas para comprender mejor su papel epigenético.

Palabras clave:
Epigenética
Degeneración macular asociada a la edad
Metilación del ADN
Patrones de metilación
Biomarcadores de la degeneración macular asociada a la edad.

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