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Introdução: A DMI é uma das principais causas de perda visual irreversível em idosos, com opções terapêuticas limitadas nas fases não avançadas, destacando a necessidade de identificar biomarcadores eficazes. Alterações epigenéticas, como a expressão das DNMTs, têm sido implicadas na DMI, mas a sua relação com mudanças estruturais na Coróide e no GCL+IPL permanece pouco explorada. Objetivo: Descrever e correlacionar a expressão genética de modeladores epigenéticos (DNMT1, DNMT3A e DNMT3B) com a espessura da Coróide e GCL+IPL, obtida através do SD-OCT em diferentes estádios de DMI. Métodos: Estudo transversal com 34 doentes distribuídos por DMI precoce (n=4), intermédia (n=13), atrófica (n=5) e neovascular (n=12). A expressão génica das DNMTs foi quantificada em sangue periférico. Foram avaliadas medidas funcionais (BCVA) e estruturais (RNFL, GCL, GCL+IPL, CRT, coroide) através de SD-OCT. Resultados: Na DMI atrófica, observou-se downregulation significativa de todas as DNMTs em comparação com fases precoce, intermédia e neovascular (p<0,05). Em contraste, verificou-se tendência para upregulation na DMI neovascular. Na DMI intermédia, níveis mais elevados de DNMT1 correlacionaram-se positivamente com espessura da GCL e do GCL+IPL central (p<0,05), enquanto DNMT3A e DNMT3B apresentaram correlações negativas com RNFL central e BCVA (p<0,05). Na DMI neovascular, a expressão de DNMT1 correlacionou-se negativamente com GCL e GCL+IPL. Conclusão: Fenótipos avançados da DMI apresentam padrões epigenéticos distintos, refletindo mecanismos patológicos diferenciados. A integração de biomarcadores epigenéticos e de imagem poderá contribuir para uma melhor estratificação da doença.
ABSTRACT: Introduction: Age-related macular degeneration (AMD) is one of the leading causes of irreversible visual loss in the elderly. Identifying effective biomarkers is essential due to the limited therapeutic options in the early stages. Epigenetic alterations, such as DNA methyltransferase (DNMT) expression, have been implicated in AMD pathogenesis; however, their association with structural changes in the choroid and GCL+IPL remains poorly understood. Objective: To describe and correlate the genetic expression of epigenetic regulators (DNMT1, DNMT3A, DNMT3B) with choroidal and GCL+IPL thickness, assessed by SD-OCT, across different stages of AMD. Methods: Cross-sectional study including 34 patients with early AMD (n=4), intermediate (n=13), atrophic (n=5), and neovascular (n=12). Gene expression of DNMTs was quantified in peripheral blood. Functional (BCVA) and structural (RNFL, GCL, GCL+IPL, CRT, choroid) parameters were assessed using SD-OCT. Results: Atrophic AMD showed significant downregulation of DNMT1, DNMT3A, and DNMT3B compared with early, intermediate, and neovascular stages (p<0.05). In contrast, neovascular AMD exhibited a trend towards DNMT upregulation. In intermediate AMD, higher DNMT1 levels correlated positively with GCL and central GCL+IPL thickness (p<0.05), whereas DNMT3A and DNMT3B correlated negatively with central RNFL and BCVA (p<0.05). In neovascular AMD, DNMT1 expression correlated negatively with GCL and GCL+IPL thickness. Conclusion: Advanced AMD phenotypes exhibit distinct epigenetic patterns, reflecting differentiated pathogenic mechanisms. Integrating epigenetic and imaging biomarkers may improve disease stratification. Larger longitudinal studies are warranted to validate these findings and to explore the potential of DNMTs as clinical biomarkers.
ABSTRACT: Introduction: Age-related macular degeneration (AMD) is one of the leading causes of irreversible visual loss in the elderly. Identifying effective biomarkers is essential due to the limited therapeutic options in the early stages. Epigenetic alterations, such as DNA methyltransferase (DNMT) expression, have been implicated in AMD pathogenesis; however, their association with structural changes in the choroid and GCL+IPL remains poorly understood. Objective: To describe and correlate the genetic expression of epigenetic regulators (DNMT1, DNMT3A, DNMT3B) with choroidal and GCL+IPL thickness, assessed by SD-OCT, across different stages of AMD. Methods: Cross-sectional study including 34 patients with early AMD (n=4), intermediate (n=13), atrophic (n=5), and neovascular (n=12). Gene expression of DNMTs was quantified in peripheral blood. Functional (BCVA) and structural (RNFL, GCL, GCL+IPL, CRT, choroid) parameters were assessed using SD-OCT. Results: Atrophic AMD showed significant downregulation of DNMT1, DNMT3A, and DNMT3B compared with early, intermediate, and neovascular stages (p<0.05). In contrast, neovascular AMD exhibited a trend towards DNMT upregulation. In intermediate AMD, higher DNMT1 levels correlated positively with GCL and central GCL+IPL thickness (p<0.05), whereas DNMT3A and DNMT3B correlated negatively with central RNFL and BCVA (p<0.05). In neovascular AMD, DNMT1 expression correlated negatively with GCL and GCL+IPL thickness. Conclusion: Advanced AMD phenotypes exhibit distinct epigenetic patterns, reflecting differentiated pathogenic mechanisms. Integrating epigenetic and imaging biomarkers may improve disease stratification. Larger longitudinal studies are warranted to validate these findings and to explore the potential of DNMTs as clinical biomarkers.
Descrição
This project was partially supported by the IDI&CA grant IPL/IDI&CA2024/INSYDE_AMD_ESTeSL, by the Health & Technology Research Center (H&TRC), Lisbon School of Health Technology (ESTeSL), Polytechnic Institute of Lisbon, and by national funding from FCT/MCTES through projects UIDP/05608/2020.
Palavras-chave
Degenerescência macular da idade Complexo de células ganglionares Coroide Epigenética DNA metiltransferases Age-related macular degeneration Ganglion cell complex Choroid Epigenetics DNA methyltransferases IPL/IDI&CA2024/INSYDE_AMD_ESTeSL FCT_UIDP/05608/2020
Contexto Educativo
Citação
Afonso A, Nobre D, Lino L, Ribeiro E, Pereira B, Ginete C, Silva C, Brito M, Camacho P. Padrões epigenéticos das DNMTs e alterações estruturais da retina na degenerescência macular da idade. RevSALUS. 2026;8(1).
Editora
Rede Academica das Ciencias da Saude da Lusofonia