Differential Effects of Elevated Hydrostatic Pressure on Gene Expression and Protein Phosphorylation in Optic Nerve Head Astrocytes

Abstract

1.1 Primary Open Angle Glaucoma (POAG) Elevated intraocular pressure (IOP) is the most important risk factor in POAG. Typically affecting older adults, in POAG the IOP exceeds the level that is tolerated by that individual’s optic nerve head (ONH). However, many individuals with clinical ocular hypertension do not exhibit glaucomatous changes in the optic disk; whereas, some individuals will develop glaucomatous changes at clinically normal IOP levels. These clinical findings indicate that individual variability in susceptibility of the ONH to IOP is an important factor in glaucomatous optic neuropathy. However, the molecular and cellular factors that may underlie variability in susceptibility of the ONH to elevated IOP have not been elucidated. The target of the mechanical stress generated by elevated IOP is the lamina cribrosa in the ONH (Bellezza et al., 2003). In the glaucomatous ONH, compression, stretching, and remodeling of the cribriform plates of the lamina cribrosa occur. In many POAG patients, these elevated IOP related changes result in remodeling of the extracellular matrix (ECM), altering the quantity and composition of several ECM macromolecules that significantly affect the biomechanical properties of the tissue supporting the nerve fibers (Hernandez, 2000; Bellezza et al., 2003). Alterations of ECM components of the ONH in glaucoma perhaps sets the stage for further optic nerve damage from IOP during the progression of the disease.