| IntroductionInfective endophthalmitis is a potentially blinding condition and remains a serious postoperative complication of such frequently performed eye surgeries as cataract or ocular trauma. Vancomycin, an antibiotic effective against all Gram -postive bacteria that interferes with cell - wall synthesis, has been increasingly recommended for the disease of Staphylococcus epiderimidis and S. aureus. endophthalmitis.Because of blood - ocular barriers, therapeutic intravitreal concen - trations of drugs can be readily achieved only by intravitreal delivery. However excessive dose of intraviteal injection of drugs can lead retinal toxicity. Laterly, the theory of glutamate can lead toxicity of nerve cell have been attented by many scholars.In order to discuss the mechanism of retinal toxicity by vancomycin , we observed the eyes that had received intravitreal injections of various concentration of vancomycin on changes of retina and glutamate levelsMaterials and Methods1. Animals New Zealand albino rabbits of other sex 96 .2. Reagents Vancomycin hydrochoride was supplied by Bli Lilly company Glutamate assay kit was supplied by JianCheng biology company in Nanjing .3. Methods In all , 96 rabbits were divided into four groups randomly . Rabbits of experimental groupl -3(n =48 for eyes for each group) were intravitreal injected concentrations 1mg/0. lml,2mg/0. 1ml,5mg/0.1ml of vancomycin respectively . Rabbits of control group ( n = 48 for eyes ) were intravitreallyinjected 0.9% sodium chloride 0. 1ml. Changes of retina were observed by ophthalmoscope , microscope and electron microscope . Concentrations of glutamate in retina were determined with UV - VIS Spectrophotometer . Six rabbits (n = 12 for eyes for each group for each day) were executed and picked off eyes at the 1,4,7and 14 day after intravitreal injection . Retina tissues of 6 of these eyes were taken for determination concentration of glutamate in retina each . The other 6 eyes were observed for changes of retina by microscope and electron microscope respectively . Factorial design was used for data stat.Results1. Observed by ophthalmoscopeThe post ocular of all eyes of control group and experimental group 1,2 were normal in all 14 days. Vitroues opacities in eyes of experimental group 3 was observed from the 3 day after intravitreal injection , reduced at the 14 day . Also retinal hemorrhage was observed.2. Observed by microscopeThe retina tissues of all eyes of control group and experimental group 1 were normal. The structures of inner and outer segment disordering lightly were observed in eyes of experimental group2 at the 7 day. The structures of retina were destroyed badly in eyes of experimental group3 .3. Observed by electron microscopeThe retina tissues of all eyes of control group and experimental groupl were normal. The cytoarchitecture of retinal inner and outer segment changed lightly in eyes of experimental group2 at the 7 day. And that the changes of structures of inner and outer segment were very obvious in eyes of experimental group3.4. Changes of glutamate levels in retina.The eyes of experimental groupl have no significant difference from of control group on glutamate levels in retina . The glutamate levels in retina had obvious increasement in the experimental group2 eyes from 4(P<0.05) to7(P< 0.01) d , which differed significantly from the levels in the control eyes . The glutamate levels in retina had obvious increasement in the experimental group3eyes from 1 to 7(P< 0.01 )d and the 14 (P<0.05)d, which differed significantly from the levels in the control eyes . The effect of time factor on the changes of glutamate levels in retina is not significant , but of dose factor is significant (P < 0. 01 ). The glutamate levels in retina in the experimental group3 eyes differed significandy from the levels in the control group , experimental groupland 2 eyes ( P < 0.01) .DiscussionGlutamate is the main neurotransmitter in Central Nervous system, which would be overly released when neuron be destroyed and bring toxicity to nervous cell . In our experiment we detected that intravitreal injection has toxicity in retina for big dose of vancomycin , with the obvious increasement of glutamate levels in retina accordingly , which make us believe that glutamate participates in the process of toxicity of vancomycin .In our experiment we detected that the effect of time factor on the changes of glutamate levels in retina is not significant , but of dose factor is significant , so we believe safe dose of drug is the key for prevention toxicity by antibiotics .In our experiment we detected that intravitreal injection has not toxicity in retina for vancomycin lmg, light toxicity for vancomycin 2mg and severe toxicity for vancomycin 5mg . Because of the effectual concentration ( > lOug/ml) of vancomycin for treatment in vitreous would be keep for 6d at least , we make suggestions that the safe dose of vancomycin for intravitreal injection is lmg/0. 1ml .In the future , we can focus research of treatment for the toxicity in retina by antibiotics on means of against glutamate .ConclusionGlutamate participates in the process of toxicity of vancomycin . To observe the glutamate levels in retina will be helpful to explore the mechanisms of toxicity in retina by antibiotics . |
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