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Editors Selection IGR 21-1

Basic Science: Hypoxia and trabecular function

Comment by Miriam Kolko on:

67489 Hypoxia-Induced Changes in DNA Methylation Alter RASAL1 and TGFβ1 Expression in Human Trabecular Meshwork Cells, McDonnell F; Irnaten M; Clark AF et al., PLoS ONE, 2016; 11: e0153354

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Although increased intraocular pressure (IOP) is not the only cause of glaucomatous neurodegeneration, IOP-lowering drugs remain the only successful treatment option. Hence, changes in the trabecular meshwork (TM) that lead to reduced outflow is an appropriate target to investigate. Fibrosis and a hypoxic environment have been associated with changes in the TM and the present study claims that changes in DNA methylation drives fibrosis in TM cells and that DNA methylation is driven by hypoxia. In order to explore their hypothesis, TM cells were isolated from control donor eyes (NTM) as well as from glaucomatous donor eyes (GTM).

DNA methylation has increasingly been the subject of intense interest because of its recognized role in various diseases. Therefore, the particular impact on DNA methylation in TM outflow needs to be confirmed by functional studies to confirm the relevance of such in glaucoma progression

Gene and protein expressions were investigated in the two groups. Finally, NTM cells were exposed to hypoxia. The study revealed different gene expression profiles in NTM cells were compared to GTM cells with regards to profibrotic transforming growth factor (TGFβ1) and antifibrotic Ras protein activator like 1 (RASAL1), both enzymes that contribute to global DNA methylation. Hypoxia resulted in similar changes in NTM cells as observed in GTM cells. In this matter, induction of DNA methylation as well as DNA Methyltransferase 1, TGFβ1 and RASAL1 expression were identified in both GTM cells as well as in NTM cells after exposure to hypoxia. The authors conclude that DNA methylation, TGFβ1 and RASAL1 appear to have an interacting relationship that may play a role in driving profibrotic disease progression in the glaucomatous TM. Overall, the study is well performed and draws attention to fibrotic changes in the TM as a future target to lower the rate of glaucoma progression. Nevertheless, DNA methylation has increasingly been the subject of intense interest because of its recognized role in various diseases. Therefore, the particular impact on DNA methylation in TM outflow needs to be confirmed by functional studies to confirm the relevance of such in glaucoma progression.

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