Segmental outflow of aqueous humor in mouse and human

Abstract

The main and only modifiable risk factor in glaucoma, the group of usually late onset progressive and irreversible blinding optic neuropathies, is elevated intraocular pressure (IOP). The increase in IOP is due to impeded aqueous humor (AH) outflow through the conventional pathway. The aberrant increased resistance at the trabecular meshwork (TM), the filter-like region in the anterior eye chamber is the major contributory factor in causing the impeded outflow. In normal as well as in glaucoma eyes the regions of the TM are divided into areas of high and low flow. The collector channels and distal outflow regions are now increasingly being recognized as potential players in contributing to impede AH outflow. Structural and molecular make-up contributing to the segmental blockage to outflow is likely to provide greater insight. Establishing segmental blockage to outflow in model systems of glaucoma such as the mouse in parallel to human eyes will expand our repertoire of tools for investigation. Further study into this area of interest has the potential to ultimately lead to the development of new therapeutics focused on lowering IOP by targeting the various components of segmental blockage of outflow in the TM and in the distal outflow region.

Keywords: Aqueous humor; Basement membrane; Extracellular matrix; Glaucoma; Intraocular pressure; Segmental outflow blockage; Trabecular meshwork.

Figure 1

Schematic depiction of segmental outflow in the anterior segment A) The ciliary processes (CB) produces aqueous humor that flows into the anterior chamber and passes through two distinct routes. The convention pathway consists of the aqueous humor passing through the trabecular meshwork (TM) into the Schlemm’s canal (SC). The unconventional pathway consists of the aqueous humor bypassing either structure. B) The trabecular meshwork (TM) consists of layers of cells in a filter-like conformation. The aqueous humor passes through the TM into the juxtacanalicular connective tissue (JCT) region then passes the inner wall (IW) of the Schlemm’s canal (SC) into collector channels (CC) and finally into episcleral veins (EV). Red arrows and their relative thickness signify the area of increasing resistance. C) Q-tracker 655 injected into the anterior chamber of 8 month old DBA/2J mice and their genetic counterpart DBA/2J-Gpnmb+/SjJ mice to depict the high flow as well as low flow areas associated with segmental outflow. At the time of these measurements IOP in DBA/2J and DBA/2-Gpnmb+-Sj/J mice eyes were 18±1 and 15±1 mg Hg respectively. Experiments were performed on n=30 (n=15 male and n= 15 females) animals for each mice strain and representative images have been presented. A notable difference is seen between the distributions of these regions in these mouse models. Blockage to outflow in the DBA/2J mice appear to be segmental consistent with findings in human glaucoma eyes.