Preconditioning provides complete protection against retinal ischemic injury in rats

Abstract

Purpose: The objectives of this study were to examine whether preconditioning can decrease ischemic damage to the retina, by electroretinographic assessment of visual function and by histologic examination of retinal structure; to investigate the time course of the effectiveness of preconditioning; and to determine whether protein synthesis is involved.

Methods: Retinal ischemia was produced for 60 minutes in anesthetized Sprague-Dawley rats. Recovery after ischemia was measured by electroretinography for a maximum period of 7 days. Retinal sections that were sliced 1 micron thick were examined 7 days after ischemia. Retinal ischemia for 5 minutes constituted the preconditioning stimulus. To assess the time course of preconditioning, animals first underwent preconditioning and then 60 minutes of ischemia 1, 24, 72, or 168 hours later; or they underwent a 5-minute sham experiment and 60 minutes of ischemia 24 hours later. An additional group of rats received 0.4 mg/kg cycloheximide, the protein synthesis inhibitor, intraperitoneally before preconditioning and underwent 60 minutes of ischemia 24 hours later.

Results: In contrast to the nonpreconditioned rats, preconditioned rats had complete recovery of the a- and b-waves compared with preischemic baseline amplitudes, and ischemia-induced histologic damage was completely 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-preconditioned rats. Severe histologic damage was also noted. Block of protein synthesis by cycloheximide completely attenuated the protective effect of preconditioning.

Conclusions: Preconditioning induces profound retinal tolerance to ischemia in vivo. The absence of a protective effect of preconditioning when there was a 1-hour or a 168-hour separation between the preconditioning stimulus and ischemia and the inhibition of preconditioning by cycloheximide support the hypothesis that a transient change in protein expression is necessary to provide this protection.