GENETIC & MOLECULAR BASIS OF PRIMARY OPEN ANGLE GLAUCOMA (POAG) PATHOGENESIS

Faisal Ahmad Lone, Ayaz Mahmood Dar*, Musharaf Rehman and Mukesh Kumar

ABSTRACT

Herein we compile the different studies regarding the cause of primary open angle glaucoma (POAG). The apoptotic theory of glaucoma suggests that ganglion cells contain protein receptors that, when activated by glutamate, increase intracellular calcium to toxic levels, forming destructive free radicals (ROS) that kill the cells. Neurotrophic nutrient deprivation theory reveals that the deprivation of vital neurotrophic nutrients for the retinal ganglion cells from the lateral geniculate nucleus. We herein also report some of the studies involving structural changes which occur in N-terminal of the myocillin involved extensive insertions and deletions while the C-terminal region involved point mutations, which may also lead to POAG. We also report herein the molecular biological studies, which suggest that mutant protein could be present through heteroaggregates in the aqueous humor (AH) and uveoscleral AH outflow of glaucoma patients that play an important role in the glaucoma pathogenesis. Another study was considered here about the endoplasmic stress that reveals that myocilin-associated POAG can be considered as an ER storage disease, occurring in steps that involves expression of misfolded and non-secreted myocilin, subsequent TM cell death. From the above evidences it might be intriguing to evaluate whether myocillin mediated ER stress induces autophagy in TM cells.

Keywords: POAG, Glaucoma, Myocillin, Mutations, Locus, ER stress.