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.T he conventional aqueous outflow pathway (CAOP) performs the dual functions of facilitating the egress of aqueous from the anterior chamber of the eye into the lumen of Schlemm's canal and of preventing the reflux of blood from the venous circulation into the anterior chamber.

The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.

The influx of Cl- across isolated frog skin bathed on the outside by 0.8 mM NaCl is about 100 nmol cm-2 h-1, which is approximately twice the Cl- influx in intact animals. The influx consists of diffusion (1%), exchange diffusion (38%), and active transport (60%). About 80% of the influx is independent of Na+ in the outer bath and is also independent of concomitant inward movement of cations. Chloride is exchanged for anions, probably HCO-3. The Cl- transport system is saturable; Vmax is about 200 nmol cm-2 h-1, and Ks is about 0.7 mM Cl-. High external concentrations of NaCl increase unidirectional fluxes of Cl- and urea, indicating a change in paracellular pathways. Active transport of Cl- is temperature sensitive (Q10 equals 2.68) and is inhibited by cyanide, dinitrophenol, iodoacetic acid, iodide, thiocyanate, and acetazolamide. The Na-independent component of JClin was unaffected by amiloride, ouabain, or eserine, all of which inhibit Na+ transport.

The APS Journal Legacy Content is the corpus of 100 years of historical scientific research from the American Physiological Society research journals. This package goes back to the first issue of each of the APS journals including the American Journal of Physiology, first published in 1898. The full text scanned images of the printed pages are easily searchable. Downloads quickly in PDF format.

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