PRECONDITIONING PROVIDES COMPLETE PROTECTION AGAINST RETINAL ISCHEMIC-INJURY IN RATS

PURPOSE. The objectives of this study were to examine whether precondi tioning can decrease ischemic damage to the retina, by electroretinogr aphic assessment of visual function and by histologic examination of r etinal structure; to investigate the time course of the effectiveness of preconditioning; and to determine whether protein synthesis is invo lved. METHODS. Retinal ischemia was produced for 60 minutes in anesthe tized Sprague-Dawley rats. Recovery after ischemia was measured by ele ctroretinography for a maximum period of 7 days. Retinal sections that were sliced 1 mu m thick were examined 7 days after ischemia. Retinal ischemia for 5 minutes constituted the preconditioning stimulus. To a ssess the time course of preconditioning, animals first underwent prec onditioning and then 60 minutes of ischemia 1, 24, 72, or 168 hours la ter; or they underwent a 5-minute sham experiment and 60 minutes of is chemia 24 hours later. An additional group of rats received 0.4 mg/kg cycloheximide, the protein synthesis inhibitor, intraperitoneally befo re preconditioning and underwent 60 minutes of ischemia 14 hours later . RESULTS. In contrast to the nonpreconditioned rats, preconditioned r ats had complete recovery of the a- and b-waves compared with preische mic baseline amplitudes, and ischemia-induced histologic damage was co mpletely prevented when preconditioning was performed 24 or 72 hours ( but not 168 hours) before ischemia. Separation of preconditioning and 60 minutes of ischemia by 1 hour caused an even greater impairment of functional retinal recovery compared with that seen in sham-preconditi oned rats. Severe histologic damage was also noted. Block of protein s ynthesis by cycloheximide completely attenuated the protective effect of preconditioning. CONCLUSIONS. Preconditioning induces profound reti nal tolerance to ischemia in vivo. The absence of a protective effect of preconditioning when there was a 1-hour or a 168-hour separation be tween the preconditioning stimulus and ischemia and the inhibition of preconditioning by cycloheximide support the hypothesis that a transie nt change in protein expression is necessary to provide this protectio n.