Retinal and Optic Nerve Degeneration After Chronic Carotid Ligation

Background and Purpose — Carotid artery disease can cause chronic retinal ischemia, resulting in transient or permanent blindness, pupillary reflex dysfunction, and retinal degeneration. This experiment investigated the effects of chronic retinal ischemia in an animal model involving permanent carotid occlusion. The time course of retinal pathology and the role of light in this pathology were examined. Methods — Sprague-Dawley rats underwent permanent bilateral occlusion of the common carotid arteries or sham surgery. Half of the animals were postsurgically housed in darkness, and half were housed in a 12-hour light/dark cycle. Animals were killed at 3, 15, and 90 days after surgery. Stereological techniques were used to count the cells of the retinal ganglion cell layer. Thy-1 immunoreactivity was assessed to specifically quantify loss of retinal ganglion cells. The thicknesses of the remaining retinal sublayers were measured. Optic nerve degeneration was quantified with the Gallyas silver staining technique. Results — Permanent bilateral occlusion of the common carotid arteries resulted in loss of the pupillary reflex to light in 58% of rats. Eyes that lost the reflex showed (1) optic nerve degeneration at 3, 15, and 90 days after surgery; (2) a reduction of retinal ganglion cell layer neurons and Thy-1 immunoreactivity by 15 and 90 days; and (3) a severe loss of photoreceptors by 90 days when postsurgically housed in the light condition only. Conclusions — Ischemic damage to the optic nerve caused loss of pupillary reflex and death of retinal ganglion cells in a subset of rats. Subsequently, light toxicity induced death of the photoreceptors.