DNA Methyltransferase Expression (DNMT1, DNMT3a, and DNMT3b) as a Potential Biomarker in Age-Related Macular Degeneration

<b>Background/Objectives:</b> Age-related macular degeneration (AMD) is a global cause of vision loss, with limited therapeutic options highlighting the need for effective biomarkers. This study aimed to characterize plasma DNA methyltransferase expression (<i>DNMT1</i>, <i>DNMT3A</i>, and <i>DNMT3B</i>) in AMD patients and explore divergent expression patterns across different stages of AMD. <b>Methods</b>: Thirty-eight AMD patients were prospectively enrolled and stratified by disease severity: eAMD, iAMD, nAMD, and aAMD. Comprehensive ophthalmological assessments were performed, including best-corrected visual acuity, digital color fundus photographs, and Spectral Domain Optical Coherence Tomography. Peripheral blood samples were collected for RNA extraction and qRT-PCR to access epigenetic effectors' transcriptional expression, namely <i>DNMT1</i>, <i>DNMT3A</i>, and <i>DNMT3B</i> genes. The collected data were analyzed using IBM SPSS 29. <b>Results:</b><i>DNMT1</i> expression was significantly downregulated in late AMD (-0.186 ± 0.341) compared to early/intermediate AMD (0.026 ± 0.246). Within late AMD, aAMD exhibited a marked downregulation of <i>DNMT1</i> (-0.375 ± 0.047) compared to nAMD (0.129 ± 0.392). <i>DNMT3A</i> and <i>DNMT3B</i> showed similar divergent expression patterns, correlating with disease stage. <b>Conclusions:</b> This study identified stage-specific transcriptional differences in <i>DNMT</i> expression, emphasizing its potential as a biomarker for AMD progression and a target for future research into personalized therapeutic strategies.