In patients with primary open angle glaucoma (POAG), the optic nerve head (ONH) shows characteristic cupping correlated with visual field defects. The progressive optic neuropathy is characterized by irreversible loss of retinal ganglion cells (RGC). The critical risk factor for axonal damage at the ONH is an elevated intraocular pressure (IOP). The increase in IOP is due to an increased resistance in the juxtacanalicular (JCT) region of the trabecular meshwork (TM) in POAG. The increased resistance can be traced back to changes in the quality and amount of the extracellular matrix (ECM). The ECM changes are very likely under control of transforming growth factor (TGF)-b2, which is found at high concentrations in the aqueous humor (AH) of patients with POAG. TGF- b2 leads to an increased synthesis of ECM molecules mediated by connective tissue growth factor (CTGF) and to an impaired ECM degradation in human trabecular meshwork (HTM) cells. Bone morphogenetic proteins (BMPs) effectively antagonize the effects of TGF- b2 on matrix deposition. Beside the changes in the TM, there are new insights that glaucoma is linked to immunological components. It was shown in the last decades that there are significant differences in the antibody profiles between glaucoma patients and control groups. Those changes also contribute to a loss of RGC in the retina.