AREAS COVERED: This paper discusses the complex process of ECM regulation in TM and explores promising therapeutic targets. The role of Transforming Growth Factor-β as a central player in ECM deposition in TM is discussed. We elaborate the key regulatory processes involved in its activation, release, signaling, and cross talk with other signaling pathways including Rho GTPase, Wnt, integrin, cytokines, and renin-angiotensin-aldosterone. Further, we summarize the therapeutic agents that have been explored to target ECM dysregulation in TM.
EXPERT OPINION: Targeting molecular pathways to reduce ECM deposition and/or enhance its degradation are of considerable significance for IOP lowering. Challenges lie in pinpointing specific targets and designing drug delivery systems to precisely interact with pathologically active/inactive signaling. Recent advances in monoclonal antibodies, fusion molecules, and vectored nanotechnology offer potential solutions.
METHODS: Scanning electron microscopy was performed on P50 and P200 devices. Bench-top flow studies were performed to find the resistances of the devices. Devices were also incorporated into a perfused, ex vivo porcine sclera model to test and compare their control of pressure, with and without overlying scleral flaps, and with trabeculectomies.
RESULTS: The luminal dimensions of the P200 device were 206.4±3.3 and 204.5±0.9 μm at the subconjunctival space and anterior chamber ends, respectively. Those of the P50 device were 205.0±5.8 and 206.9±3.7 μm, respectively. There were no significant differences between the P200 and P50 devices (all P>0.05). The resistances of the P200 and P50 devices were 0.010±0.001 and 0.054±0.002 mm Hg/μL/min, respectively (P<0.05). Equilibrium pressures with overlying scleral flaps were 17.81±3.30 mm Hg for the P50, 17.31±4.24 mm Hg for the P200, and 16.28±6.67 mm Hg for trabeculectomies (P=0.850).
CONCLUSIONS: The luminal diameters of both devices are externally similar. The effective luminal diameter of the P50 is much larger than 50 μm. Both devices have low resistance values, making them unlikely to prevent hypotony on their own. They lead to similar equilibrium pressures as the trabeculectomy procedure when inserted under the scleral flap.
METHODS: The model exploits the principle of dynamic and geometric similarity, so while dimensions were up to 30× greater than actual, the flow had similar properties. Scleral flaps were represented by transparent 0.8- and 1.6-mm-thick silicone sheets on an acrylic plate. Dyed 98% glycerin, representing the aqueous humor was pumped between the sheet and plate, and the equilibrium pressure measured with a pressure transducer. Image analysis based on the principle of dye dilution was performed using MATLAB software.
RESULTS: The pressure drop across the flap was larger with thinner flaps, due to reduced rigidity and resistance. Doubling the surface area of flaps and reducing the number of sutures from 5 to 3 or 2 also resulted in larger pressure drops. Flow direction was affected mainly by suture number and position, it was less toward the sutures and more toward the nearest free edge of the flap. Posterior flow of aqueous humor was promoted by placing sutures along the sides while leaving the posterior edge free.
CONCLUSION: We demonstrate a new physical model which shows how changes in scleral flap thickness and shape, and suture number and position affect pressure and flow in a trabeculectomy.