Trimethyltin induced pathology in sensory neurons.

Pathologic changes in the retina, inner ear, pyriform cortex, olfactory tubercle, and dorsal root ganglia as a result of trimethyltin (TMT) intoxication were investigated. Long-Evans rats were orally intubated with TMT chloride at a dose of 6.0 mg TMT/kg b.w. Swelling of the optic fiber layer and necrotic changes in the ganglion and inner nuclear layers were observed in the retina as early as 72 hours after intoxication. Large segments of the retina were devoid of ganglion cells at later posttreatment times. The inner ear was also found to be extremely vulnerable to the toxicity of TMT. Edematous swelling of the hair cells and vacuolar changes of the spiral ganglion cells in the Organ of Corti were observed 24 hours after TMT exposure. Extensive destruction of these structures was evident 15-30 days after intoxication. Small neurons in the olfactory cortex (pyriform cortex and olfactory tubercle) also degenerated rapidly after TMT exposure. Electron microscopy demonstrated lysosomal accumulation and vacuolar changes in these nerve cells. Extensive destruction of both the pyriform cortex and olfactory cortex was observed 15 days after exposure. Although no necrotic change was observed in the neurons of the dorsal root ganglia, electron microscopy revealed extensive accumulation of lysosomes and formation of myeloid bodies both in the neuronal bodies and dorsal root fibers. Vacuolar breakdown and dissolution of the Nissl substance were found in some neurons. Thirty days after treatment, hypertrophy and hyperplasia of the neuronal mitochondria were observed. Such a change was believed to represent a compensatory response by these organelles. These findings provide the first morphological evidence of neuronal damage in the sensory neurons of both the central and peripheral nervous system following acute TMT administration.