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The mechanism by which laser trabeculoplasty lowers intraocular pressure remains unknown. Roberts et al. (850) present an intriguing hypothesis to explain how laser irradiation of the trabecular meshwork can increase the hydraulic conductivity (HC) across the cells lining the juxtacanalicular tissue (JCT). They propose that laser energy acts by two effects on the TM. The first is the destructive arm in which there is damage to the anterior region of the TM. The second is the therapeutic arm in which there is enhancement of outflow at the JCT, which includes juxtacanalicular TM cells, extracellular matrix, and the inner wall of Schlemm's canal. To test their hypothesis, they studied the HC of cultured human TM cells using in vitro models of semiconductor diode laser treatment in two flow apparatuses. They showed that viable cell monolayers (after laser treatment) demonstrated increased HC and non-viable monolayers (representing 'over-treated' cells) exhibited a decrease in HC. In a second set of experiments, viable laser-treated cells showed a statistically significantly increased HC compared with control cell monolayers. In vitro models for physiological and molecular processes have inherent limitations which also apply in this case. For example, there is a presumption that the behavior of the cultured TM cells represents that of TM cells lining the JCT. Most if not all of the cultured TM cells are anterior cells due to the nature of the dissection. The inability to culture a pure population of JCT TM cells represents a significant limitation in many cultured TM studies. Furthermore, treatment-related alterations in fluid flow across TM cells grown on filter supports (as used in this study) may only represent the effects on inter-cellular and trans-cellular resistance. What about potential effects on the ECM? Or endothelial cells lining the inner wall of Schlemm's canal? Future studies to validate or test the hypotheses presented by the authors may wish to correlate changes in HC to pigmentation of the TM cells (Latina et al. Exp Eye Res 1995; 6: 359-371) and the production of cytokines, metalloproteinases, and tissue inhibitors of metalloproteinases (TIMPs) (Hosseini et al. IOVS 2006; 47: 1469-1476; Parshley et al. Curr Eye Res 1995; 14: 537-544), as well as histological and immunohistological findings. In summary, the authors present a very interesting theory for the mechanism by which laser trabeculoplasty works, and future studies in vitro and in vivo may support this theory.