**1. Introduction**

Glaucoma is a heterogenous disease with numerous contributing factors including environment, genetics, and epigenetics. It is the primary cause of irreversible blindness in the world and the number of patients diagnosed is only projected to increase in the coming years. The use of preclinical animal models has exponentially progressed our understanding of the underlying pathophysiology of the disease, as well as providing a platform for generating and testing successful therapeutics. This chapter delves into the fundamentals of glaucoma including the pathologies, types, and symptoms with a subsequent description of the numerous preclinical animal models of the disease and what has been garnered from their study. We will then discuss treatments of glaucoma that are either FDA-approved or in development and conclude by summarizing how pre-clinical studies have advanced the development of new glaucoma therapeutics.

## **1.1 Basics of glaucoma**

The eye is an elaborate structure suited to performing its unique function: collecting photons of light and converting that to an electrical signal allowing for vision. Because light needs to enter the eye without impedance, the cornea and lens lack vasculature. However, a source of nutrients and waste efflux is necessary for tissue survival. This necessity is answered by way of the aqueous humor, a waterbased filtrate of the blood produced by the ciliary body of the eye. As it flows from the ciliary body through the pupil, the aqueous humor carries and bathes the tissues with sugars, vitamins, and other necessary supplies for cellular survival while carrying the excreted cellular metabolic waste products back to the blood stream for removal. The exit path for the aqueous humor is through the trabecular meshwork, Schlemm's canal and supplementary outflow structures (**Figure 1A**). Any imbalance between aqueous humor production and its elimination can have an impact on intraocular pressure (IOP). As they exit the eye, the axons of retinal ganglion cells (RGCs) converge and they become the nerve fibers of the optic nerve (**Figure 1B**) [1]. RGC axon degeneration can be induced by both elevated IOP-related changes and IOP-independent factors.

Glaucoma, defined as pathological damage to the optic nerve (ON), results in visual field defects due to death of the retinal ganglion cells (RGCs) and damage to their axons. Glaucoma is the leading cause of irreversible blindness globally. Trends predict that by 2040, as many as 111.8 million people worldwide will have this disease [2]. Of the approximately 80 million current cases, 11 million are estimated to result in complete blindness [3]. Glaucoma's primary risk factor is elevated intraocular pressure (IOP), although some forms of this disease do not include this endophenotype.

This disease is classified into the conventional categories of primary openangle glaucoma (POAG) and primary angle-closure glaucoma (PACG), as well as primary congenital glaucoma, normotensive glaucoma (NTG), and pigmentary dispersion glaucoma. Other rare types exist, such as exfoliation glaucoma and traumatic glaucoma. The most important modifiable risk factor for onset and progression of glaucoma is elevated IOP, although normotensive glaucoma patients suffer from vision loss in spite of their IOP being in the normal physiological range, highlighting the complexity of this disease. In other subtypes of

#### **Figure 1.**

*Aqueous humor dynamics and retinal ganglion cells: two areas of glaucoma-related research. (A) The aqueous humor is produced by the ciliary body and exits through the trabecular meshwork and other outflow structures leaving the eye and entering the blood stream (flow shown in blue). (B) The axons of the retinal ganglion cells (blue) form the optic nerve and run through the lamina cribosa as they exit the eye. In glaucoma, retinal ganglion cells and their axons can be damaged due to IOP-related or IOP-independent mechanisms. Figures modified from Li, et al. 2012. Courtesy: National Eye Institute, National Institutes of Health.*

### *An Overview of Glaucoma: Bidirectional Translation between Humans and Pre-Clinical… DOI: http://dx.doi.org/10.5772/intechopen.97145*

this disease, glaucoma can also result from a variety of IOP-related mechanisms due to structural alterations that inhibit outflow of aqueous humor. These include trabecular meshwork obstruction by foreign material, trabecular endothelial cell loss, loss of phagocytic activity of the trabecular meshwork, loss of giant vacuoles from the endothelium of Schlemm's canal and reduced pore size or density in the wall of Schlemm's canal [4].
