**1.2 Pathophysiology of glaucoma**

In the early stages of glaucoma, glial cells in the optic nerve head respond to glaucomatous change. IOP-related mechanisms of damage generally include obstruction of the trabecular meshwork, morphological changes in astrocytes such as enlargement of cell body and processes, as well as upregulation of cytoskeletal and extracellular matrix proteins. Studies have demonstrated that remodeling of astrocytes and increased deposition of extracellular matrix can occur in some forms of experimental glaucoma. Moreover, even a short period of IOP elevation can cause hypertrophy, process retraction, and simplification of the shape of astrocytes in the optic nerve without changes in gene expression. In addition, the accompanying extracellular matrix deposition is believed to be an early defense mechanism to repair or prevent damage to the blood retina barrier [5]. In later stages of glaucoma, glial scar formation can occur as a reaction to injury as a method of protection and healing. Glial cells recruit immune cells, increasing extracellular matrix deposition and inflammatory factors that prevent axonal regeneration [6].

Interestingly, different compartments of RGCs and the optic nerve die by different cellular mechanisms. Specifically, if the RGC axon is cut, the axon distal to the lesion degenerates via Wallerian degeneration, while the axon proximal to the lesion is removed by a process called dying back. Lastly, the cell body of the axon dies via apoptosis [7, 8]. All of which occur among glial scar formation. This process of RGC axon loss can be observed *in situ* during a dilated pupil fundus examination. This area of the posterior globe is termed the optic disc with its center termed the optic cup. Damage from glaucoma causes destruction of the nerve fibers around the rim of this structure and increases the size of the "cup"; an increase in the cup-todisc ratio is one of the clinical phenotypes that is used to clinically monitor disease progression.
