摘要
目的评估膦甲酸钠前房和玻璃体腔注射对角膜及视网膜的毒性。方法选取成年新西兰白兔36只,采用随机数字表法将其随机分为对照组、玻璃体腔注药组和前房注药组,每组12只,其中对照组一侧眼玻璃体腔注射0.1 ml平衡盐溶液(BSS),另一侧眼前房内注射等容积BSS;玻璃体腔注药组和前房注药组分别于单眼玻璃体腔和前房内注射0.1 ml膦甲酸钠1.2 mg。于注射后第1、7、14、28天分别对3只实验兔进行裂隙灯显微镜、检眼镜、光学相干断层扫描、活体扫描共聚焦显微镜检查,处死后摘取双眼眼球分别对角膜及视网膜行光学显微镜、扫描电子显微镜和透射电子显微镜检查,综合评估膦甲酸钠对角膜和视网膜的毒性。结果裂隙灯显微镜、光学相干断层扫描结果显示,玻璃体腔注药组和对照组均未见角膜水肿、眼内炎症或其他异常。前房注药组注射后1 d可见角膜轻度水肿,注射后7 d角膜水肿消退。活体扫描共聚焦显微镜结果显示,玻璃体腔注药组和前房注药组角膜内皮细胞呈典型六边形,未见形态学异常。玻璃体腔注射BSS组、前房注射BSS组、玻璃体腔注药组和前房注药组注药前和注药后1、7、14 d ECD总体比较差异均无统计学意义(F_(分组)=1.21,P=0.32;F_(时间)=1.21,P=0.32)。光学显微镜下观察结果显示,各组注药后不同时间点角膜形态学均未见明显异常。玻璃体腔注药组和前房注药组注射后1和7 d均可见视网膜神经纤维层空泡化,伴大量炎性细胞浸润。玻璃体腔注射BSS组注射后1 d神经纤维层内也出现炎症细胞浸润,但未见空泡化改变。光感受器层无结构改变,细胞核层组织良好。扫描电子显微镜下观察结果显示,玻璃体腔注药组注射后1 d角膜内皮未见明显异常。前房注药组注射后1 d可见大量炎性细胞沉积并黏附在角膜内皮上,注射后7 d消失。透射电子显微镜下观察结果显示,玻璃体腔注药组注射后1 d角膜内皮细胞肿胀,内质网扩张,部分线粒体肿胀,注射后14 d恢复正常;注射后1 d,视网膜神经纤维层可见泡状结构,注射后28 d仍有组织间液残留。前房注药组注射后1 d可见角膜内皮细胞线粒体和内质网肿胀,14 d后恢复正常;注射后1 d视网膜外节膜盘结构异常,视神经纤维层产生组织间液,至注射后28 d未完全恢复。结论膦甲酸钠前房和玻璃体腔注射对视网膜有短暂毒性作用,随时间延长作用逐渐减弱。膦甲酸钠前房内注药对角膜内皮细胞的毒性作用较玻璃体腔内注药更显著。
Objective To evaluate the toxicity of foscarnet sodium injection into the anterior chamber and intravitreal cavity on the cornea and retina.Methods Thirty-six adult New Zealand White rabbits were randomly divided into control group,intravitreal injection group,and intracameral injection group,with 12 rabbits in each group.In the control group,0.1 ml of balanced salt solution(BSS)was injected into the vitreous cavity of one eye,and an equal volume of BSS was injected into the anterior chamber of the other eye.In the intracameral injection group and intravitreal injection group,0.1 ml of sodium foscarnet 1.2 mg was injected into the anterior chamber and vitreous cavity of one eye,respectively.Slit-lamp microscopy,ophthalmoscope,optical coherence tomography(OCT),and in vivo confocal laser scanning microscopy were performed on 3 experimental rabbits from each group on days 1,7,14,and 28 after injection.After sacrifice,both eyeballs were removed,and the corneas and retinas were examined using optical microscopy,scanning electron microscopy and transmission electron microscopy to evaluate the toxicity to the cornea and retina comprehensively.The use and care of the animals complied with the ARVO Statement.The study protocol was approved by an Ethics Committee of Peking University Third Hospital(No.IRB00006761-2015197).Results Slit-lamp microscopy and OCT showed no corneal edema,intraocular inflammation,or other abnormalities in the intravitreal injection and control groups.Mild corneal edema was observed in intracameral injection group 1 day after injection,which resolved 7 days after injection.In vivo confocal laser scanning microscopy revealed normal hexagonal corneal endothelial cell morphology in the intravitreal injection and control groups.There was no significant difference in endothelial cell density at baseline and 1,7,and 14 days after injection among the three groups(F_(group)=1.21,P=0.32;F_(time)=1.21,P=0.32).Light microscopy revealed no obvious corneal abnormalities.On days 1 and 7 after injection,retinal nerve fiber layer vacuolization and inflammatory cell infiltration were observed in the intravitreal injection and control groups.In the intravitreal injection of BSS group,inflammatory cell infiltration occurred in the retina without vacuolization 1 day after injection.There were no structural changes in the photoreceptor layer,and the nuclear layer was well-organized.Scanning electron microscopy showed no significant abnormalities in the corneal endothelium in the intravitreal injection group 1 day after injection.In the intracameral injection group,a large number of inflammatory cells were deposited and adhered to the corneal endothelium 1 day after injection and disappeared 7 days after injection.Transmission electron microscopy revealed that in the intravitreal injection group,1 day after injection swelling of corneal endothelial cells,dilatation of the endoplasmic reticulum,and partial mitochondrial swelling were observed,which normalized 14 days after injection and vacuolization was present in the retina and interstitial fluid accumulation persisted until the 28 days after injection.In the intracameral injection group,swollen mitochondrial and endoplasmic reticulum of corneal endothelial cells was observed and resolved by 14 days after injection.However,structural abnormalities in the membranous discs of the photoreceptor outer segments and interstitial fluid accumulation in the optic nerve fiber layer persisted 1 day after injection and did not fully recover 28 days after injection.Conclusions Intracameral intravitreal and injection of foscarnet sodium have transient toxic effects on the retina,which gradually weaken over time.Intracameral injection of foscarnet sodium was more toxic to corneal endothelial cells than intravitreal injection.
作者
赵英涵
孙彬佳
卢青
李晨迪
余婷
洪晶
彭荣梅
Zhao Yinghan;Sun Binjia;Lu Qing;Li Chendi;Yu Ting;Hong Jing;Peng Rongmei(Department of Ophthalmology,Peking University Third Hospital,Beijing 100191,China)
出处
《中华实验眼科杂志(中英文)》
北大核心
2025年第8期713-721,共9页
Chinese Journal Of Experimental Ophthalmology
基金
国家自然科学基金(81800801、31271045、81650027)。
关键词
膦甲酸钠
玻璃体腔注药
前房注药
药物毒性
角膜
视网膜
Foscarnet sodium
Intravitreal injections
Intracameral injection
Toxicity
Cornea
Retina
