RT Journal Article
SR Electronic
T1 A new insight into the cellular regulation of aqueous outflow: how trabecular meshwork endothelial cells drive a mechanism that regulates the permeability of Schlemm’s canal endothelial cells
JF British Journal of Ophthalmology
JO Br J Ophthalmol
FD BMJ Publishing Group Ltd.
SP 1500
OP 1505
DO 10.1136/bjo.2005.081307
VO 89
IS 11
A1 J A Alvarado
A1 R G Alvarado
A1 R F Yeh
A1 L Franse-Carman
A1 G R Marcellino
A1 M J Brownstein
YR 2005
UL http://bjo.bmj.com/content/89/11/1500.abstract
AB Aim: To test 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. Methods: The TMEs were first irradiated with a laser light and allowed to condition the medium, which is then added to SCEs. The treatment response is determined by both measuring SCE permeability (flow meters) and the differential expression of genes (Affymetrix chips and quantitative polymerase chain reaction (PCR)). The cytokines secreted by the treated cells were identified using ELISA and the ability of these cytokines to increase permeability is tested directly after their addition to SCEs in perfusion experiments. Results: SCEs exposed to medium conditioned by the light activated TMEs (TME-cm) respond by undergoing a differential expression (DE) of 1120 genes relative to controls. This response is intense relative to a DE of only 12 genes in lasered SCEs. The TME-cm treatment of SCEs increased the SCE permeability fourfold. The role of 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. 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. This novel TME driven cellular mechanism has important implications for the pathogenesis of glaucoma and the mechanism of action of laser trabeculoplasty. Ligands identified as regulating SCE permeability have potential use for glaucoma therapy.