Research for associations of tension-dependent aqueous outflow regulation by trabecular meshwork with glaucoma pathology.

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To identify factors associated with the tension-dependency, we developed a pressure model by using three-dimension culture of trabecular meshwork cells. In this model, collagen, medium, and cells were mixed and then were stabilized by changing the pH. After letting cells migrate and proliferate in the model, the model was weighed, and cells in the model were observed by immunostaining. F-actin was found to be decreased by observation with the confocal microscopy. Considering ROCK inhibitors which decrease F-actin could lower intraocular pressure in human, we assumed that this response contributed to the homeostasis of intraocular pressure by using the same mechanism with ROCK inhibitors. It was difficult, however, to approach proteins in cells in the three-dimension culture. We therefore assessed the reaction of trabecular cells against oxidative stress, because we speculated that the intracellular reaction against pressure stress had similar aspects with that against oxidative stress. After exposure to oxidative stress, the Akt-PI3K signaling and the p38 signaling in the trabecular meshwork cells were revealed to be activated. Moreover, oxidative stress-induced cell death was enhanced by inhibiting these signalings. These novel findings provided us a valuable clue to understanding the mechanisms that regulate aqueous humor outflow.