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New Insight Into the Cellular Regulation of Aqueous Outflow
A study published in the British Journal of Ophthalmology focused on testing the hypothesis that trabecular meshwork endothelial cells (TMEs) increase the permeability of Schlemm's canal endothelial cells (SCEs) by actively releasing ligands that modulate the barrier properties of SCEs. The TMEs were first irradiated with a laser light and allowed to condition the medium, which was then added to the SCEs. The human-cultured TMEs and SCEs used for this experiment were grown and maintained in cell culture conditions.
The treatment response was determined by measuring SCE permeability (flow meters) and the differential expression of genes (Affymetrix chips and quantitative polymerase chain reaction). The cytokines secreted by the treated cells were identified using enzyme-linked immunosorbent assay and the ability of these cytokines to increase permeability was tested directly after their addition to SCEs in perfusion experiments.
Investigators found that SCEs exposed to medium conditioned by the light activated TMEs (TME-cm) responded by undergoing a differential expression (DE) of 1120 genes relative to the controls. This response is intense relative to a DE of only 212 genes in lasered SCEs. The TME-cm treatment of SCEs increased the SCE permeability four-fold. The role of the cytokines in these responses is supported by two findings: adding specific cytokines established to be secreted by lasered TMEs to SCEs increases permeability; and inactivating the TME-cm by boiling or diluting abrogates these conditioned media permeability effects.
In conclusion, these experiments show that TMEs can regulate SCE permeability and that it is likely that TMEs have a major role in the regulation of aqueous outflow.