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The Anti-proliferative Effect of Paclitaxel Polylactic Acid Microsphere on Scarring of Filtering Passageways in Rabbit Eyes after Trabeculectomy

Author: ChiJing
Tutor: MaXiaoHua
School: Shandong University of Traditional Chinese Medicine
Course: Ophthalmology
Keywords: Paclitaxel polylactic acid microspheres Trabeculectomy Sustained-release Antiproliferative Bleb Cells and fibrous proliferation Security
CLC: R779.6
Type: Master's thesis
Year: 2011
Downloads: 13
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Abstract

Objective: To investigate the paclitaxel polylactic acid microspheres in the rabbit after trabeculectomy antiproliferative effect their safety evaluation. Method: (1) using high performance liquid chromatography (HPLC) method paclitaxel polylactic acid microspheres in the release time of the aqueous humor release effect was observed in the aqueous humor. ② 48 healthy adult rabbits build glaucoma filtration surgery animals were randomly divided into four groups: blank control group, the standard control group, the experimental group Ⅰ and experimental group Ⅱ right eye underwent standard trabeculectomy; preoperative The experimental group Ⅱ line F-ERG fundus examination to rule out eye problems, and each group of the cornea, conjunctiva, anterior chamber, crystals, fundus, intraocular pressure. Each group corresponds to the surgical site under the scleral flap surgery medication, 0.3mg/ml mitomycin C (MMC), and 0.3mg/ml paclitaxel 5min and placed between the conjunctiva and sclera of the experimental group II 2.5mg paclitaxel polylactic acid microspheres. The ③ filtering bleb the Kronfeld standard genotyping [1]. Compare 7,21,35,49 the number of days in each group functional blebs after surgery. Groups IOP the ④ measuring preoperative and postoperative 7,21,35,49 days and record the data for statistical analysis, comparing each group at each time point IOP difference. (5) histopathology: 21,35,49 days after each group were randomly taken from four rabbits eye removal has surgery, take the bleb and around corneoscleral tissue, fixed paraffin sections do hematoxylin - eosin (HE) staining, light microscopy filtration canal open and the number of inflammatory cells; to do immunohistochemistry of proliferating cell nuclear antigen (PCNA) staining, fibroblast proliferation was observed; doing Masson trichrome staining filter aisle newborn proliferation of collagen fibers. ⑥ postoperatively with slit lamp possible complications in each group: conjunctival wound leak, punctate corneal epithelial shedding, shallow anterior chamber, anterior chamber inflammation, lens opacities, thin-walled blebs; observed by indirect ophthalmoscopy no fundus harm. The ⑦ paclitaxel polylactic acid microspheres safety evaluation: 12 rabbits 7,21,35,49 days after biomicroscopy to observe whether the conjunctival wound leakage, corneal epithelial punctate shedding, shallow anterior chamber anterior chamber inflammation and other complications, with an indirect ophthalmoscope fundus observe security organization paclitaxel polylactic acid microspheres eye; were preoperative and postoperative day 7,21,35,49 line corneal endothelial microscopic examination and F-ERG examination, were observed paclitaxel polylactic acid microspheres on the corneal endothelium, retinal toxicity; and the rabbits were sacrificed after 49 days, take the surgical site corresponding to the cornea, anterior chamber angle, anterior lens capsule The transmission electron microscope examination of the tissue was observed paclitaxel polylactic acid microspheres angle trabecular meshwork endothelial cells and lens epithelial cells on the corneal endothelium. Results: ① room Determination of drug content in the water that paclitaxel polylactic acid microspheres in sustained action, maintain a high level of concentration of the drug in the body over an extended period; ② The after seven days the number of groups functional blebs basically the same; 21,35,49 days after the blank control group functional bleb are four groups in the lowest number of standard control group and the experimental group Ⅰ functional filtration was no significant difference in the number of bulbs; experiment II group postoperative time point the number of functional bleb significantly more than the other three groups; ③ The after seven days the four groups IOP basically the same (P gt; 0.05); experimental II group after each time point IOP were lower than the other three groups (P lt; 0.05); standard control group and the experimental group Ⅰ postoperative intraocular pressure at each time point is basically the same (P gt; 0.05), no significant difference; postoperative days 21,35,49 intraocular pressure of the blank control group than in the other three groups (P lt; 0.05), a significant difference; ④ four groups of seven days after histopathological no significant difference; 21,35,49 days after the experimental group Ⅱ HE The number of fibroblast proliferation and Masson trichrome staining showed that most of the filtration canal open in good condition, less the number of inflammatory cells of PCNA staining showed the number of proliferation of new collagen fibers than those of the other three groups less; postoperative time point HE staining, PCNA immune group staining, Masson trichrome staining results, the antiproliferative effect of the standard control group and the experimental group Ⅰ was no significant difference, gradually increased with the development of time, the proliferation of cells and fibers in filtration canal; surgery filtration canal after the first 21 days of the blank control group differences in proliferation compared with the other three groups, and as time goes on, this difference is more and more obvious, filtration canal after 49 days have been completely blocked. ⑤ postoperative complications: standard control group rabbit eye conjunctival wound leakage and the phenomenon of shallow anterior chamber; standard control group and the experimental group Ⅰ rabbit eyes corneal epithelial punctate shedding the thin-walled bleb phenomenon, these concurrent The disease healed after a few days, and found no abnormalities. The standard control group after the rabbit eyes the crystal slightly turbid phenomenon. Blank control group after severe anterior chamber inflammation, prone to shallow anterior chamber; experimental II group at each time point of the postoperative anterior chamber inflammation than those of the other three groups of light. ⑥ paclitaxel polylactic acid microspheres safety evaluation results: Slit lamp examination: paclitaxel polylactic acid microspheres eye organizations not produce significant complications; fundus examination found no abnormalities; postoperative examination showed F-ERG ERG latent when and volatility did not change significantly compared with the preoperative; microscopic examination of corneal endothelial cells display paclitaxel polylactic acid microspheres did not change significantly the indicators of endothelial cell density and cell area coefficient of variation; transmission electron microscopy results show that, compared with the control eyes, paclitaxel poly acid microspheres on the corneal endothelium, angle trabecular meshwork endothelial cells, lens epithelial cells without significant side effects. Paclitaxel polylactic acid microspheres before used in surgery after 60Co radiation sterilization to achieve the requirements of sterile surgery, can be used in surgery. Conclusion: In this study, preparation of paclitaxel polylactic acid microspheres in the aqueous humor concentration of the drug in a long period of time to maintain a higher level in sustained action; biocompatibility, no significant side effects; surgery in conjunctiva and sclera between the surgical site implantation can effectively inhibit inflammatory cells, proliferation of fibroblasts and new collagen fibers, contribute to the formation of functional bleb, to maintain the patency of the filtration channel, effectively reducing IOP; simultaneously , which is applied to the eye, having a certain degree of security, not intraocular tissue harmful. Therefore, paclitaxel polylactic acid microspheres is expected to become a new secondary glaucoma filtration surgery antiproliferative drugs.

The Anti-proliferative Effect of Paclitaxel Polylactic Acid Microsphere on Scarring of Filtering Passageways in Rabbit Eyes after Trabeculectomy

Abstract

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