Optic nerve diseases are among the most devastating disorders in ophthalmology leading to retinal ganglion cell (RGC) degeneration, visual field loss and, potentially, blindness. The pathophysiologic mechanisms underlying optic neuropathies are not fully understood, although research in this area is substantial. Animal models are required in order to investigate the mechanism of each disease in detail, to improve our knowledge of how and why optic nerve axons die, and to test new treatment modalities. Developing an animal model for a disease, however, is usually complicated and challenging, and most experimental models are remote from the human disease. There are several animal species that can be developed as suitable models for human disease. The advantage of using a monkey is its close phylogeny and high homology with humans. Monkeys have retinal and optic nerve anatomy that is nearly identical to human eyes. The validity of the experimental model, however, depends upon the degree to which it emulates the human condition, and a primate model is considered as having the closest compatibility for conducting research with the goal of understanding human diseases. Indeed, testing new treatment modalities in a monkey model is usually the last step before embarking upon clinical trials in humans. Unfortunately, monkeys are very expensive, their availability is limited, and they are difficult to handle. Experiments in monkeys require highly experienced teams and special housing facilities, making them beyond the reach of many research laboratories. Thus, rats and mice are commonly used to investigate optic nerve diseases. There is great conservation between rats, mice, and human genomes, which allows them to be widely used for research on human optic nerve disease. 1 Rats are inexpensive, easy to house and handle, and their eyes, optic nerves, and superior colliculus are easily accessible. The structures of their optic nerve and retina, however, have a number of differences from those of humans: the eyes of rats and mice do not have maculae or foveae and 85–90% of their optic nerve axons decussate to the other side of the brain. While rats are commonly used to study optic nerve injuries, the availability of a mouse model confers unique advantages. Genetic studies in mice are proving to be a potent means for learning about genes and pathologic mechanisms that cause disease. In addition, the genome of the mouse can be altered by adding transgenes or altering endogenous genes. Laboratory mice live for approximately 2 years and often develop diseases that take decades to develop in humans. Models of optic nerve disease in the mouse can enable us to study the mechanism of RGC degeneration and potential new therapies using genetic manipulation in various transgenic and knockout mice that are not available in rats. 2