Post-treatment at 12 or 18 hours with 3-aminobenzamide ameliorates retinalischemia-reperfusion damage

PURPOSE. The window of protection afforded by 3-aminobenzamide (3-ABA), a p oly(ADP-ribose) polymerase (PARP) inhibitor, against apoptotic loss of inne r retinal elements after ischemia-reperfusion insult in mts was examined. METHODS. Ischemia-reperfusion injury to the retinas in albino Lewis rats wa s induced by elevated intraocular pressure (IOP) through cannulation of the anterior chamber with a needle connected to a saline column delivering a p ressure of 110 mm Hg. The ischemic period was held at 60 minutes, and reper fusion was established immediately afterward. 3-Aminobenzamide (3-ABA) was administered intravitreally at 0, 4, 8, 12, 18, or 24 hours after reperfusi on and its effect evaluated by morphology and morphometry of the inner reti nas at 7 days after reperfusion. Immunohistochemistry of poly-(ADP-ribose), a product of PARP activity, and Western blot analysis for PARP were perfor med on retinas at 0, 4, 8, 12, 18, and 24 hours after reperfusion. RESULTS. Morphology and morphometry showed significantly better preserved i nner retinas in animals receiving 3-ABA between 12 and 18 hours after reper fusion. Immunohistochemical study of poly(ADP-ribose) showed elevated level s at the retinal ganglion cell layer and the inner nuclear layer at 12 and 18 hours after reperfusion. Western blot analysis of PARP showed a notable increase in the 116-kDa band (PARP) from 4 to 18 hours after reperfusion. CONCLUSIONS. Administration of 3-ABA at 12 or 18 hours after ischemia, when there was accumulation of poly-(ADP-ribose) in the inner retina, significa ntly ameliorated retinal ischemia-reperfusion injury. These findings, toget her with earlier reports from our laboratory, are consistent with a late an d pivotal role of PARP in apoptotic loss of inner retinal elements after is chemia-reperfusion insult to the retina.