Eyeworld

EW GLAUCOMA 28 June 2018 by Liz Hillman EyeWorld Senior Staff Writer Glaucoma editor's corner of the world Researchers hope to better understand glaucoma disease pathogenesis T here are a lot of potential drug targets for glauco- ma that have not been addressed due to a poor understanding of the pathogenesis of various forms of the disease, according to Yutao Liu, PhD, Department of Cellular Biolo- gy and Anatomy, Medical College of Georgia, Augusta University, Augus- ta, Georgia. That's why Dr. Liu sees value in looking at the epigenetics in patient samples that might help identify something new. In a study pub- lished in Human Molecular Genetics, Dr. Liu and a team of researchers from several domestic and interna- tional universities and institutions identified microRNA (miRNA) profiles in the aqueous humor of patients with primary open angle glaucoma (POAG) and patients with exfoliation glaucoma that seemed to be unique in the aqueous humor to each disease. 1 Dr. Liu said this research could not only help pave the way for a better understanding of what is causing these diseases but also establish better drug targets for therapy. As noted in the Drewry et al. paper, previous research has asso- ciated miRNAs, small, non-coding RNA molecules that regulate gene expression, to glaucoma, and others have analyzed the presence of miRNAs in aqueous humor of glaucoma patients compared to patients without glaucoma. The research by Drewry et al. sought to improve upon previous research by analyzing miRNA from the aqueous humor of 12 patients with POAG and 12 with exfoliation glaucoma (pseudoexfoliation glaucoma), separately, under the assumption that the two are "distinctly different diseases." The researchers also used direct digital detection to count miRNA without amplification. Dr. Liu explained that amplification could inaccurately represent the amount of miRNA in a sample and could add to the background noise. NanoString Human v3 (NanoString Technologies, Seattle), the system Molecules in aqueous humor could identify new drug targets for glaucoma I n this issue's "Glaucoma editor's corner of the world," we take a look at glaucoma epi- genetics. Epigenetics is the study of phenotype changes that are caused by modification of gene expression rather than changes in the genes themselves. How does this occur? DNA methylation and histone modification are a few mechanisms. Consider the following: Folic acid, a vitamin found in green, leafy vegetables, is also a methyl donor that can be used (as a reagent) in DNA methylation. Methylated DNA will be expressed differently than non-methylat- ed DNA. Like any reagent, having fewer methyl donors (folate molecules) around will result in less DNA methylation, and that is how your diet can affect the expression of your genes. But how could this play out in glaucoma? In this article, Yutao Liu, PhD, speaks about microRNA differences between POAG and exfoliation glaucoma subjects. Exfoliation has been associated with elevated homocysteine levels. As you will read, a different epigenetic signa- ture emerged when comparing aqueous humor samples from POAG and exfoliation syndrome eyes. You could imagine a number of reasons why gene expression would differ between POAG and exfoliation glaucoma. In exfoliation glaucoma, we get the sense that the outflow pathway is blocked, and IOP is elevated with resulting pressure-related stress and potentially compen- satory (epigenetic) mechanisms. With POAG, perhaps the eye has an underlying weakness or susceptibility to damage. While a few genes have been uncovered in POAG, perhaps an interplay between biomechanical weaknesses and gene expression occurs and advances the pathophysiology. Join us as we learn about what lies above genes, literally policing the expression of these genes, and how this may interact with glaucoma. Nathan Radcliffe, MD, Glaucoma editor

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