关键词: 曲安奈德, 视网膜, 毒性, 线粒体, 溶媒, 兔

Abstract:  Objective To evaluate the effects of triamcinolone acetonide(TA) crystals on the rabbit retina. Design Experimental study. Participants Twenty-one New Zealand white rabbits. Method The animals were divided into group A (Crystal A), B (Crystal B) and C (balanced salt solution, BBS). Group A was divided into subgroup A1, A2 and A3; group B was divided into subgroup B1 and B2, and group C was divided into subgroup C1 and C2. Crystal A and B were purified by centrifugation from two commercial TA injections. The right eyes in subgroup A1, A2, A3 were injected intravitreally with Crystal A of 4 mg, 20 mg and 40 mg, respectively; the right eyes in subgroup B1 and B2 were injected with Crystal B of 4 mg and 20 mg, respectively; the right eyes in subgroup C1 and C2 were injected with 0.1 ml and 0.2 ml BBS respectively as control. Retina structure was examined by light microscope(LM) and transmission electron microscope(TEM).  Main Outcome Measures Fundal morphology, retina structure under LM and TEM structures of photoreceptors. Results At 8 weeks after injection, none of the eyes showed abnormalities in anterior segments and fundus. LM examinations showed that retina structures in injected eyes of group C and group A appeared normal comparing with the eyes without injection, while in the injected eyes of group B, inner and outer retinal structure disorganization was noted, with subgroup B2 showing more obvious changes. TEM examinations showed that eyes in subgroup C1 and C2 showed edema of the photoreceptor mitochondriae with cristae disruption, whereas nuclei and discs of the photoreceptors appeared normal. In subgroup A1, A2 and A3, slight edema of the photoreceptor discs was shown, while nuclei and mitochondriae appeared normal structure; Furthermore, the mitochondriaes were shown to be more orderly arranged as dose increased, which suggested a potential dose-dependent protective effect. Comparing with the uninjected eyes and the injected eyes in group A and C, the injected eyes in group B showed marked changes such as edema of the photoreceptor discs and mitochondriae, and pyknosis and karyolysis of photoeceptor nuclei. The eyes in subgroup B2 showed more remarkable disorganization than the eyes in group B1. Conclusion The two commercial TA crystals show differential effects on the rabbit retina. Both products show dose-related toxic effects to retinal sturcture, which might be induced by vehicle components. Whether the therapeutic benefit outweighs the potential toxicity should be determined before clinical application. Some products may produce potential protective effects on photoreceptor mitochondria, which needs to be proved in the further investigations.

Key words: triamcinolone acetonide, retina, toxicity, mitochondria, vehicle, rabbit