Glaucoma of the brain: a disease model for the study of transsynaptic neural degeneration

Abstract

The identification of mechanisms precipitating neuronal death and injury is an intense area of investigation requiring reliable models to assess the effects of neuroprotective agents. Most are suboptimal since the effects of initial damage are diffuse and may not be reproducible or easily quantifiable. The ideal laboratory model should have the ability to (a) clearly detect evidence of neuronal injury and recovery, (b) accurately measure morphologically the extent of these changes, and (c) provide functional evidence for damage and recovery. Glaucoma is a disease of visual neurons in the eye and brain. In the visual system, neuroanatomical pathways and retinotopic organization are exquisitely defined, functional modalities are highly characterized and can be dissected physiologically, visual input parameters can be modified, visual functional output can be readily tested and measured, changes in the eye and the visual brain can be directly visualized and imaged, and pathological and compensatory changes in brain centers of vision can be examined and measured specifically. For these reasons, the glaucoma disease model is ideal for the study of response and recovery to injury in the central nervous system due to anterograde and retrograde degeneration from the eye to the brain and the brain to the eye, respectively. The study of this glaucoma model of transsynaptic brain injury may be relevant to understanding more complex pathways and point to new strategies to prevent disease progression in other neurodegenerative diseases.