Intraocular pressure homeostasis: maintaining balance in a high-pressure environment

Abstract

Although glaucoma is a relatively common blinding disease, most people do not develop glaucoma. A robust intraocular pressure (IOP) homeostatic mechanism keeps ocular pressures within relatively narrow acceptable bounds throughout most peoples' lives. The trabecular meshwork and/or Schlemm's canal inner wall cells respond to sustained IOP elevation and adjust the aqueous humor outflow resistance to restore IOP to acceptable levels. It appears that the cells sense IOP elevations as mechanical stretch or distortion of the actual outflow resistance and respond by initiating a complex extracellular matrix (ECM) turnover process that takes several days to complete. Although considerable information pertinent to this process is available, many aspects of the IOP homeostatic process remain to be elucidated. Components and mechanisms beyond ECM turnover could also be relevant to IOP homeostasis, but will not be addressed in detail here. Known aspects of the IOP homeostasis process as well as possible ways that it might function and impact glaucoma are discussed.

FIG. 1.

Schematic of typical intraocular pressure (IOP) homeostatic response. Constant flow perfusion of human anterior segment organ cultures for 48 h at 1×flow rate followed by sustained perfusion at 2×flow rate during which time, the outflow system adjusts the outflow resistance to restore normal pressure.

FIG. 2.

IOP homeostatic response to 2×pressure. Human anterior segment organ cultures subjected to constant pressure perfusion at 1×pressure for 48 h followed by perfusion at 2×pressure. Normalized outflow facility is plotted for 23 separate experiments. Mean facility before homeostatic corrections (1×) was 0.34 μL/min/mm Hg and significance (***) was assessed by one-way ANOVA with the Dunnett's Multiple Comparison Test.