Prior optic nerve transection reduces capsaicin-induced degeneration in rat subcortical visual structures

Capsaicin is a neurotoxin capable of causing degeneration in specific sites throughout the neuraxis, including the suprachiasmatic nucleus (SCh), the ventrolateral geniculate nucleus (VLG), the intergeniculate leaflet (IGL), and the olivary and medial pretectal nuclei (OPT and MPT). In this experiment, we tested the hypothesis that capsaicin-induced terminal degeneration in the SCh, VLG, IGL, OPT, and MPT results from destruction of retinal ganglion cells and their axonal projections to these sites. In the first experiment, silver stains were used to examine degeneration in the retina induced by systemic capsaicin treatment. Capsaicin caused degeneration of ganglion cells, bipolar cells, and nerve terminals in the retina, which could be observed between 2 and 24 hours after treatment. In the second experiment, 15-day-old rat pups were enucleated unilaterally. Five days or 2, 5, or 10 months later, they were injected systemically with capsaicin and killed 6 hours (pups) or 18 hours (adults) later for analysis with a cupric silver stain. In rats of all ages, prior monocular enucleation reduced or eliminated capsaicin-induced degeneration in the contralateral SCh, VLG, IGL, OPT, and MPT. In the third experiment, rat pups were treated systemically with capsaicin or vehicle solution at 12 days of age and given unilateral intravitreal injections of cholera toxin conjugated to horseradish peroxidase (CT-HRP) 3 days prior to sacrifice at 20 days of age. Transport of CT-HRP to the SCh, VLG, IGL, MPT, and OPT was attenuated but not abolished by capsaicin pretreatment. Results suggest that capsaicin causes degeneration in the SCh, VLG, IGL, MPT, and OPT by selective destruction of a subpopulation of retinal ganglion cells with axonal projections to these sites.