聚乙烯醇(PVA)水凝胶填充兔玻璃体腔的安全性及有效性研究

Safety and efficacy of filling the vitreous cavity with polyvinyl alcohol hydrogel in rabbits

目的评价30 g·L(-1)聚乙烯醇(polyvinyl alcohol,PVA)水凝胶在兔玻璃体腔内长期填充的安全性与有效性。方法将新西兰白兔12只随机分为2组:PVA水凝胶组(PVA组)6只、BSS组6只。2组兔右眼行三通道玻璃体切割术,切除玻璃体后分别填充PVA水凝胶和BSS溶液。术后行裂隙灯、眼底镜、眼压、B超和眼底照相检查;术后90 d、180 d行视网膜电流图(electroretinogram,ERG)检查,同时处死兔并摘出眼球,收集眼内PVA水凝胶后行流变学检查,眼球送病理学检查。结果至观察终期PVA组与BSS组术眼的角膜、前房等均无明显异常;PVA组有2眼并发白内障、BSS组有1眼并发白内障,2组术眼均未见玻璃体积血、混浊、增殖,视网膜脱离,脉络膜脱离等并发症出现。眼压情况:术前及术后3 d、7 d、14 d、30 d、60 d、90 d和180 d,两组间各时间点眼压比较差异均无统计学意义(均为P>0.05)。ERG检查提示2组术眼SkotERG和PhotERG的a波、b波峰值与术前相比,差异均无统计学意义(均为P>0.05),两组间比较差异亦均无统计学意义(均为P>0.05)。眼球固定切片和HE染色,光镜下显示:2组术眼视网膜全层结构完整,内丛状层和外丛状层连续,内、外核层细胞排列整齐,视网膜全层细胞未见明显炎症、变性、坏死等改变。电镜下观察显示:术后90 d视网膜色素上皮细胞线粒体轻度水肿、结构欠清,周围有PVA高分子物附着;而术后180 d线粒体细胞水肿明显加重、结构更加模糊。PVA水凝胶在术后90 d玻璃体腔内仍填充较饱满,未见明显降解,黏弹性能未见明显改变,而在术后180 d玻璃体腔内的PVA水凝胶水样物增多,出现明显降解,黏弹性能显著降低。结论 30 g·L(-1) PVA水凝胶在体内有良好的生物相容性和视网膜支撑功能,但长期填充后容易被降解。

Objective To evaluate the safety and efficacy of using 30 g·L-1 polyvinyl alcohol(PVA)hydrogel to fill in the vitreous cavity of rabbits in a long term.Methods Totally 12 New Zealand white rabbits were randomly divided into 2 groups:6 in PVA hydrogel group(PVA group)and 6 in BSS group.The right eye of each rabbit in the two groups underwent a three-channel vitrectomy.After that,PVA hydrogel and BSS solution were filled respectively.After surgery,the eye was examined by the slit lamp,ophthalmoscope,ultrasound,and fundus photography.And the intraocular pressure was tested.On day 90 and day 180 after surgery,the electroretinogram(ERG)was performed.At the same time,the rabbit was sacrificed and the PVA hydrogel in the eye was collected for rheology examination.And the eyeball was sent for pathological examination.Results By the end of observation,there was no obvious abnormalities in the cornea and anterior chamber in PVA group or BSS group.Two eyes were complicated with cataract in PVA group.One eye was complicated with cataract in BSS group.None of the eyes in the two groups had developed complications such as hemorrhage,opacity and proliferation of vitreous body,or detachment of retina or choroid.As for the intraocular pressure,there was no significant difference between the two groups at each time point,as before surgery and the 3rd,7th,14th,30th,60th,90th and 180th day after surgery(all P>0.05).ERG examination of the two groups showed that there were no significant differences of the post-operative peaks of wave a and wave b in SkotERG and PhotERG comparing with the pre-operative peaks(all P>0.05).After fixation,sectioning and HE staining,the eyeball was examined by light microscope:All retinal lamina of the two groups were intact.The inner and outer plexiform laminas were continuous.The inner and outer nuclear laminas were arranged neatly.All retinal lamina showed no obvious changes like inflammation,degeneration,and necrosis and so on.Examination by electron microscope:On the 90th day after surgery,the mitochondria in retinal pigment epithelium were slightly swollen,with blurry structures and appended by polymeric PVA.On the 180th day after surgery,the mitochondria were more severely swollen,with blurrier structures.On the 90th day after surgery,the vitreous cavity was still full of PVA hydrogel,without obvious signs of degradation or changes of viscoelasticity.However,on the 180th day after surgery,The PVA hydrogel became watery in the vitreous body,with obvious degradation and decreased viscoelasticity.Conclusion PVA hydrogel(30 g·L-1)has a satisfactory biocompatibility and retinal supporting function in vivo,but can be degraded after filling for a long term.