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- DNA methyltransferase expression (DNMT1, DNMT3a and DNMT3b) as a potential biomarker for anti-VEGF diabetic macular edema responsePublication . Camacho, Pedro; Ribeiro, Edna; Pereira, Bruno; Varandas, Teresa; Nascimento, João; Henriques, José; Dutra-Medeiros, Marco; Delgadinho, Mariana; Oliveira, Ketlyn; Silva, Carina; Brito, MiguelPurpose: DNA methylation is involved in Diabetic Retinopathy progression showing a metabolic memory mechanism. However, the association of DNA methyltransferase with diabetic macular edema is still unknown. We aimed to describe the differences in DNA methyltransferase gene expression in patients with different diabetic macular edema responses. Methods: A total of 27 diabetic patients, aged 59-90 years, were prospectively enrolled in this cross-sectional study. The participants were classified into the control group (CG, n = 11), diabetic macular edema responders (rDME, n = 9), and non-responder diabetic macular edema (nrDME, n = 7) after anti-vascular endothelial growth factor (anti-VEGF) treatment. Only cases with a complete ophthalmological examination, digital 133° color fundus, and SD-OCT assessments were used. After RNA extraction and first-strand cDNA synthesis, quantitative real-time PCR was performed with specific primers on the CFX Connect™ Real-Time PCR Detection System to assess differential transcriptional expression patterns. Results: The DNMT1 gene showed a positive correlation (r = 0.617; p = 0.043) with Best Corrected Visual Acuity (BCVA) in CG, a positive correlation (r = 0.917; p = 0.010) with HbA1c in nrDME and a negative correlation (r = -0.659; p = 0.049) with GCL-IPL thickness in rDME. DNMT3A gene showed a positive correlation (r = -0.890; p = 0.001) with Sub-foveal Choroidal thickness in rDME whereas DNMT3b gene showed a negative correlation (r = -0.815; p = 0.007) with HbA1c and RNFL (r = -0.664; p = 0.026) in CG. Conclusions: Patients with similar metabolic profile risk factors showed associated DNA methyltransferase transcriptional expression patterns differences fitting with the anti-VEGF diabetic macular edema response. Further studies are needed to clarify if these results (1) reflect disease evolution, (2) translate the therapeutic impact, (3) or can help to predict the therapeutic resistance profile.
- DNA methylation in diabetic macular edema: first reportPublication . Camacho, Pedro; Pereira, Bruno; Ribeiro, Edna; Varandas, T.; Henriques, J.; Nascimento, J.; Dutra-Medeiros, M.; Ribeiro, C.; Delgadinho, Mariana; Oliveira, Ketlyn; Silva, Carina; Brito, MiguelEnvelhecimento humano e estilos de vida tem contribuído para aumento da DM. Edema macular diabético (EMD), uma das manifestações oculares da RD, é a principal causa de perda de visão em pessoas diabéticas. 30-40% casos EMD não respondem da melhor forma aos AVEGF (loading phase). Resistência pode persistir após 12 meses tratamento (+/50%). Objetivo do estudo: Desenvolver uma caracterização multimodal não invasiva (SD OCT e OCT A) combinada com a avaliação da metilação de DNA de forma a pode esclarecer alguns mecanismos importantes da doença mas também para novas abordagens terapêuticas que contribuem para a medicina de precisão.
- Role of DNA methylation in persistent diabetic macular edemaPublication . Camacho, Pedro; Pereira, Bruno; Ribeiro, Edna; Varandas, Teresa; Henriques, José; Nascimento, João; Dutra-Medeiros, Marco; Silva, Carina; Delgadinho, Mariana; Oliveira, Ketlyn; Brito, MiguelBackground: a) Disease duration and metabolic control are insufficient to understand Diabetic Macular Edema (DME), the leading cause of vision loss in people with diabetes; b) 30-40% of cases of DME do not respond optimally to AVEGF (loading phase); c) poor genetic association in DR development (<25% RD) and PDR progression (25-50%). Purpose: To study the role of DNA methyltransferase expression (DNMT1,DNMT3a, DNMT3b) in persistent diabetic macular edema.