ABSTRACT
Optic neuropathies are chronic neurodegenerative diseases of the optic nerve [1-3], in which degeneration of the axons leads eventually to death of their corresponding cell bodies, the retinal ganglion cells (RGCs). The mechanism underlying the progression of disease is not yet fully understood but probably involves the activity of physiological compounds that become cytotoxic when their normal concentrations are exceeded. In order to study the mechanisms of RGC death, identify the nerve-derived mediators of toxicity causing the ongoing spread of damage, and screen compounds for their neuroprotective potential (i.e., their ability to arrest or reduce this secondary degeneration), suitable animal models are needed. We have established a rat model in which the optic nerve is subjected to a well-calibrated partial crush injury of the required severity [4,5]. Use of the model has made it possible to demonstrate self-propagating secondary degeneration [5], identify some of the mediators of degeneration common to many neurodegenerative disorders [6], study the molecular mechanisms underlying RGC death, and discover processes of neuroprotection [7-12]. Molecular mechanisms can also be studied in the severely crushed optic nerve of the mouse, an easily obtained model in which the availability of transgenic mice can be exploited for studies of the effects of relevant genes on RGC survival [13,14].
