Toxic-nutritional optic neuropathy in cuba: Histological and immunohistochemical analysis of the retina and the nerve fiber layer

Purpose. An epidemic of optic neuropathy with a demonstrated toxic-nutritional etiology affected Cubans between 1992 and 1993. This study evaluated the histologie changes in the retina and optic nerve head from the eye of a patient afflicted by the epidemic. Methods. We examined the retina of a 43-y.o. female who was diagnosed with the optic form of the Cuban epidemic and who died of unrelated causes during the acute stage of the optic neuropathy. The tissues were processed immediately after death and embedded in paraffin. 5-nm thick sections were stained with hematoxilin-eosin for light microscope examination of the retinal layers, immunoperoxidase with neurofilament protein staining for neurofilament and axonal details, and KJenow DNA fragmentation detection for cellular apoplosis. All results were compared with an age-matched control. Results. There was a marked decrease in the number of ganglion cells in the macular area with a clear reduction in the thickness of the nerve fiber layer while no damage was observed in the photoreceptor and bipolar layers. Some of the remaining ganglion cells showed nuclear chromatolysis. These observations were confirmed and amplified by neurofilament protein staining which demonstrated a reduced band of neurofilament proteins in the inner plexi form layer and an absence of staining of the nerve fiber layer in the papillomacular bundle. The Klenow DNA fragmentation detection labeled a large number of ganglion cells and a few photo receptors. Concision. These data suggest that in the Cuban toxic-nutritional optic neuropathy, the insults were directed at the axonal component of the eye. In fact, the appearance of nuclear chromatolysis in many of the remaining ganglion cells supports the idea that the primary site of damage in this disease is the axon. These findings are in agreement with our other studies of toxic-metabolic neuropathy in which disrupted oxidative phosphorylation resulting in axonal death has been suggested as the cause of pathology. The posiiivc staining for apoplosis may indicate a reactive, but programmed, response by the axons to a threshold of loxic-nutritional insult.