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Editors Selection IGR 16-4
Basic Science: Trabecular molecular biology
Comment by Rachel Kuchtey on:
60729 Mapping molecular differences and extracellular matrix gene expression in segmental outflow pathways of the human ocular trabecular meshwork, Vranka JA; Bradley JM; Yang YF et al., PLoS ONE, 2015; 10: e0122483
Although intraocular pressure (IOP) reduction remains the only proven therapeutic approach in treating glaucoma patients, and despite the fact that the pathological site of IOP dysregulation, namely trabecular meshwork (TM) and Schlemm's canal, has been known for many decades, no anti-glaucoma medications directly target the diseased region. This is largely due to the lack of understanding of aqueous humor outflow regulation.
The evidence of complexity of segmental flow of aqueous humor in the TM is beautifully presented in the study.
Segmental flow of aqueous humor, characterized by high and low flow regions within the TM is a well-known phenomenon, however, neither the significance of this observation nor the underlying mechanisms is known. In this study, Vranka and co-workers rigorously tested different fluorescently labeled microspheres to define different flow regions of TM using well-established human anterior segment organ culture. With robust methods, the investigators not only confirmed segmental flow of aqueous humor in the TM, they also elegantly demonstrated such pattern on both a macro- and micro-scale. The labeling system also allowed the authors to investigate the distribution of collector channels in the high and low flow regions. Interestingly, no differential distribution was seen. Using quantitative PCR arrays, the authors reported a number of extracellular matrix genes differentially expressed in the high and low flow regions of the TM. Although some differential protein levels in different regions were evident, matrix metalloproteinase (MMP) proteolytic enzyme activity was similar in high and low flow regions. The authors speculate this finding was largely due to the fact they used non-specific MMP substrate for the assay. The evidence of complexity of segmental flow of aqueous humor in the TM is beautifully presented in the study. However, the clinical significance of the findings remains elusive. Would targeting the specific region with specific flow pattern, either with pharmacological agents or surgical approach, be the future treatment of lowing IOP?
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