A Model for Graded Retinal Ischemia in Rats

PURPOSE: Retinal ischemic injury depends on grade and duration of an ischemic insult. We developed a method to induce ischemic injury in rats permitting: (1) Variable grades of retinal blood flow (F) reduction, (2) controllable duration of F reduction, (3) injury without collateral neural damage, and (4) optical measurements of F and O(2)-related factors: O(2) delivery (DO(2)), O(2) extraction fraction (OEF), and metabolic rate of O(2) (MO(2)). METHODS: In five anesthetized rats the left common carotid artery (CA) was ligated and the right CA was exposed. A variable clamp having a backstop and a rod mounted on a micromanipulator straddled the right CA. Advancing the rod with the micromanipulator produced graded compressions of the CA. F and O(2)-related factors were measured with established optical techniques. RESULTS: Four to seven grades of F for at least 10 minutes were achieved per rat. F decreased only with compressions of over 60%. DO(2) changed in proportion to F, particularly at low F. As F decreased, OEF initially changed little, but then rose steeply to its maximum of 1 when F was approximately 4 μL/min. MO(2) was stable with reduced F until OEF maximized, after which it decreased progressively. CONCLUSIONS: This model in rats permits acute, graded inner retinal ischemia that is reversible after prescribed durations, does not otherwise injure the eye and allows optical measurement of important physiologic factors during ischemia. TRANSLATIONAL RELEVANCE: This model will allow improved understanding of retinal ischemic injury and enable better management of this common, sight-threatening affliction.