To evaluate the apoptosis-enhancing effect of intravitreal bevacizumab on retinal photoreceptor cells and protective effect of l-carnitine

Purpose: To evaluate the apoptotic effect of intravitreal bevacizumab on retinal photoreceptor cells in rabbits and to demonstrate if L-carnitine prevents this probable apoptotic effect.Methods: Thirty male rabbits (New Zealand, albino) weighing 2 to 3 kg each were used in this study. All rabbits` right eyes underwent intravitreal bevacizumab of either 2 mg (0,08 ml), 4 mg (0,16 ml) or 6 mg (0,24 ml). 15 rabbits underwent intraperitoneal 500 mg/kg L-carnitine additionally. All rabbits? left eyes, which had the same amount of intravitreal saline solution with their right eyes, were tested as control. Rabbits? eyes were observed daily for two weeks. After two weeks, rabbits were sacrificated and globs were enucleated. Enucleated eyes were preserved for light microscopic, electron microscopic and immunuhistochemistrical investigation.Results: During the follow-up period, cornea and the lens remained unchanged, no retinal complications were detected. In both enjection and control eyes there was no significant retinal toxicity in histolgical sections which were performed by hematoxylin and eosin (H&E) staining. Ultrastructural damage, DNA fragmantation and caspase?3 immunostaining in all intravitreal bevacizumab groups were observed with electron microscopy, immunohistochemical method and TUNEL method. The ultrastructural damages in 2 and 4 mg intravitreal bevacizumab groups were mild but serious in 6 mg intravitreal bevacizumab group. No cellular damage was detected in 2 and 4 mg intravitreal bevacizumab groups which underwent intraperitoneal L-carnitine additionally. There was no significant difference in cellular damage in both 6 mg intravitreal bevacizumab groups with or without additional intraperitoneal L-carnitine.Conclusion: Intravitreal bevacizumab causes apoptotic effects on retinal photoreceptor cells with all doses of intravitreal bevacizumab. Intraperitoneal L-carnitine could prevent this damage in 2 and 4 mg intravitreal bevacizumab groups despite this results there was no inhibiting effect of L-carnitine on apoptotic damage in 6 mg intravitreal becizumab group.Key words: Age-related macular degeneration, apoptosis, Intravitreal bevacizumab, L-carnitine, VEGF inhibition