Immunological and molecular basics of the primary open angle glaucoma pathomechanism

Abstract

Glaucoma is a degenerative process of the optic nerve. Increased intraocular pressure is believed to be the main factor leading to the glaucomatous damage. The in vitro and in vivo animal glaucoma research models provide insight into the molecular changes in the retina in response to the injury factor. The damage is a complex process incorporating molecular and immunological changes. Such changes involve NF kB activity and complement activation. The processes affect the human antigen, JNK, MAPK, p53, MT2 and DBA/2J molecular pathways, activate the autophagy processes and compromise neuroprotective mechanisms. Activation and inhibition of immunological responses contribute to cell injury. The immunological mechanisms of glaucomatous degeneration include glial response, the complement, tumor necrosis factor α (TNF-α) pathways and toll-like receptors athways. Oxidative stress and excitotoxicity are factors contributing to cell death in glaucoma. The authors present an up-to-date review of the mechanisms involved and update on research focusing on a possible innovative glaucoma treatment.

Keywords: apoptosis; autophagy; complement; glaucoma; oxidative stress; retinal ganglion cells (RGCs).

Fig. 1

Oxidative stress. The reduced oxygen supply leads to increase in production of reactive oxygen species (ROS) and their inefficient elimination. ROS activate HIF-1α that targets HSP-27, erythropoietin and vascular endothelial growth factor elevation

Fig. 2

Excitotoxicity in retinal ganglion cell (RGCs) death. Glutamate, in presence of co-ligand (glycine or D-serine), binds to trans-membrane N-methyl-D-aspartate receptor. It enables Ca2+ influx into the soma of the RGCs, which enhances the death signals

Fig. 3

Intrinsic apoptotic pathway. Description in the text

Fig. 4

Extrinsic apoptotic pathway. Description in the text