Effect of persistent high intraocular pressure on microstructure and hydraulic permeability of trabecular meshwork**Project supported by the National Natural Science Foundation of China (Grant Nos. 31070840, 10802053, and 81201123), the Natural Science Foundation of Beijing, China (Grant No. 3122010), the Natural Science Foundation of Guangdong Province, China (Grant No. S2012040006576), the Shenzhen Science and Technology Innovation Committee, China (Grant No.

Abstract

As the aqueous humor leaves the eye, it first passes through the trabecular meshwork (TM). Increased flow resistance in this region causes elevation of intraocular pressure (IOP), which leads to the occurrence of glaucoma. To quantitatively evaluate the effect of high IOP on the configuration and hydraulic permeability of the TM, second harmonic generation (SHG) microscopy was used to image the microstructures of the TM and adjacent tissues in control (normal) and high IOP conditions. Enucleated rabbit eyes were perfused at a pressure of 60 mmHg to achieve the high IOP. Through the anterior chamber of the eye, in situ images were obtained from different depths beneath the surface of the TM. Porosity and specific surface area of the TM in control and high IOP conditions were then calculated to estimate the effect of the high pressure on the permeability of tissue in different depths. We further photographed the histological sections of the TM and compared the in situ images. The following results were obtained in the control condition, where the region of depth was less than 55 μm with crossed branching beams and large pores in the superficial TM. The deeper meshwork is a silk-like tissue with abundant fluorescence separating the small size of pores. The total thickness of pathway tissues composed of TM and juxtacanalicular (JCT) is more than 100 μm. After putting a high pressure on the inner wall of the eye, the TM region progressively collapses and decreases to be less than 40 μm. Fibers of the TM became dense, and the porosity at 34 μm in the high IOP condition is comparable to that at 105 μm in the control condition. As a consequent result, the permeability of the superficial TM decreases rapidly from 120 μm2 to 49.6 μm2 and that of deeper TM decreases from 1.66 μm2 to 0.57 μm2. Heterogeneity reflected by descent in permeability reduces from 12.4 μm of the control condition to 3.74 μm of the high IOP condition. The persistently high IOP makes the TM region collapse from its normal state, in which the collagen fibers of the TM are arranged in regular to maintain the physiological permeability of the outflow pathway. In the scope of pathologically high IOP, the microstructure of the TM is sensitive to pressure and hydraulic permeability can be significantly affected by IOP.