|Anti-proliferation effects of Sirolimus sustained delivery film in rabbit glaucoma filtration surgery|
|Yan, Zhi-chao1; Bai, Yu-jing2,3; Tian, Zhen3; Hu, Hai-yan4; You, Xiu-hua4; Lin, Jian-xian3; Liu, Shao-rui1; Zhuo, Ye-hong3; Luo, Rong-jiang1|
|WOS标题词||Science & Technology|
|类目[WOS]||Biochemistry & Molecular Biology ; Ophthalmology|
|研究领域[WOS]||Biochemistry & Molecular Biology ; Ophthalmology|
|关键词[WOS]||TARGETED DRUG-DELIVERY ; FILTERING SURGERY ; BIODEGRADABLE POLYMERS ; ANIMAL-MODEL ; TRABECULECTOMY ; 5-FLUOROURACIL ; RAPAMYCIN ; IMPLANT ; RELEASE ; GROWTH|
Purpose: To investigate the efficacy, safety, and mechanisms of Sirolimus sustained delivery film on prevention of scar formation in a rabbit model of glaucoma filtration surgery.
Methods: Sixty-four New Zealand white rabbits who underwent trabeculectomy in the right eye were randomly allocated to one of the four treatment regimens: Sirolimus sustained delivery film treatment group (Group A), or drug-free film treatment group (Group B), or 30 ng/ml Sirolimus-soaked sponge treatment group (Group C), or no adjunctive treatment group (Group D), and each group consists of 16 rabbits. Intraocular pressure (IOP), morphologic changes of bleb, anterior chamber flare, and corneal endothelial cell count and complications were evaluated over a 28-day period follow-up time. Aqueous humor samples were gathered from Group A, and the concentration of Sirolimus was measured regularly post-operation. Rabbits were sacrificed on the 7th, 14th, and 28th day post-operation separately, and the fibroblast hypertrophy, infiltration of inflammatory, and proliferation of new collagen fiber formation in each group were evaluated with HE and Masson staining. Proliferative cell nuclear antigen (PCNA) and fibroblast apoptosis were evaluated by immunohistochemistry and terminal deoxynucleotidyl transferasemediated dUTP nick end labeling (TUNEL) assay at the 28th day post-operation.
Results: Both Sirolimus sustained delivery film (Group A) and Sirolimus alone (Group C) were well tolerated in this model, and significantly prolonged bleb survival compared with no drug treatment group (Group B and D; p<0.001). Group A had the longest bleb survival time in comparison with other groups (p<0.001). There were significant differences in IOP readings between Group A and other groups at the last follow-up (p<0.05). The concentration of Group A maintained stable for over 2 weeks, drops from (10.56 +/- 0.05) ng/ml at day 3 to (7.74 +/- 0.05) ng/ml at day 14. The number of corneal endothelial cells of Group A was not statistically significant between pre and post-operation. Histologic examination demonstrated that eyes treated with Sirolimus, especially the Sirolimus sustained delivery film, showed an obvious reduction in subconjunctival fibroblast scar tissue formation compared with no drug treatment groups, and had minimal evidence of inflammatory cell infiltration and new collagen deposition in the subconjunctiva. Immunohistochemistry assay showed that PCNA-expression was lower in the Group A (16.25 +/- 3.24%) compared to other groups (p<0.01). TUNEL assay showed a significant increase in the number of apoptotic fibroblasts around the surgical area in Group A and Group C (9.75 +/- 1.71% and 8.50 +/- 1.92%) compared to the Group B and D (p<0.01).
Conclusions: Sirolimus drug sustained delivery film can inhibit inflammatory cell activity, impede fibroblast proliferation activity, and induce fibroblast apoptosis in the filtration surgery sites in rabbit. The results indicate a safe and effective treatment strategy in anti-scaring treatment in glaucoma surgery.
|项目编号||2008B030301083 ; 30872832|
|资助机构||Science and Technology Planning Project of Guangdong Province to R.L., China ; Guangdong Province Universities ; National Natural Science Foundation of China|
|作者单位||1.Sun Yat Sen Univ, Affiliated Hosp 1, Dept Ophthalmol, Guangzhou 510080, Guangdong, Peoples R China|
2.Peking Univ, Peoples Hosp, Dept Ophthalmol, Key Lab Vis Loss & Restorat,Minist Educ, Beijing 100871, Peoples R China
3.Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Lab Ophthalmol, Guangzhou 510080, Guangdong, Peoples R China
4.Sun Yat Sen Univ, Sch Pharmaceut Sci, Res & Dev Ctr Pharmaceut, Guangzhou 510080, Guangdong, Peoples R China
|Yan, Zhi-chao,Bai, Yu-jing,Tian, Zhen,et al. Anti-proliferation effects of Sirolimus sustained delivery film in rabbit glaucoma filtration surgery[J]. MOLECULAR VISION,2011,17(270-71):2495-2506.|
|APA||Yan, Zhi-chao.,Bai, Yu-jing.,Tian, Zhen.,Hu, Hai-yan.,You, Xiu-hua.,...&Luo, Rong-jiang.(2011).Anti-proliferation effects of Sirolimus sustained delivery film in rabbit glaucoma filtration surgery.MOLECULAR VISION,17(270-71),2495-2506.|
|MLA||Yan, Zhi-chao,et al."Anti-proliferation effects of Sirolimus sustained delivery film in rabbit glaucoma filtration surgery".MOLECULAR VISION 17.270-71(2011):2495-2506.|