The role of axoplasmic transport in the pathogenesis of retinal cotton-wool spots.

Small retinal arterioles in the pig retina were occluded by argon laser photocoagulation and the morphology and topography of the resulting lesions studied by ophthalmoscopy, histology, and electron microscopy. Two days after laser coagulation ischaemic necrosis of the inner retina was observed in the territory of occluded arterioles, and swollen axon terminals packed with cytoplasmic organelles were found in the retinal nerve-fibre layer on the peripheral border of the infarcts and their border nearest to the disc. These swellings gave rise to localised zones of opacification (cotton-wool spots) at the borders of the retinal infarcts, and similar zones developed in relation to the laser burns. Amino-acid uptake and transport in retinal ganglion cells was studied in these animals by autoradiography following an intravitreal injection of tritiated leucine. When 3H-leucine was injected at the same time as laser coagulation and arteriolar occlusion, label became concentrated in the swollen axon-terminals on the peripheral aspect of 2-day-old infarcts but was absent from the terminals on the disc side of infarcts. The accumulation of 3H-leucine and organelles was attributed to interruption of orthograde axoplasmic transport. When 3H-leucine was injected into the vitreous 2 days prior to laser occlusion, label became distributed throughout the axoplasm and then accumulated in swollen axon terminals on both sides of infarcts after a further 2 days. An obstruction to both orthograde and retrograde axoplasmic flow was thus demonstrated. We concluded that cotton-wood spots should be redefined as accumulations of cytoplasmic debris in the retinal nerve-fibre layer caused by obstruction of orthograde or retrograde axoplasmic transport in ganglion cell axons.