TGF-β_2反义寡核苷酸抑制抗青光眼术后滤过泡瘢痕的实验研究  

Experimental study of TGF-β_2 antisense oligodeoxynucleotide as a anti-scarring agent in glaucoma surgery

作　　者：李金瑛[1] 傅培[2] 黎晓新[1] 

机构地区：[1]北京大学人民医院眼科,博士研究生现在100000 [2]北京大学深圳医院眼科

出　　处：《眼科研究》2006年第3期277-280,共4页Chinese Ophthalmic Research

基　　金：深圳市科技局资助项目(JH200505300483B)

摘　　要：目的观察TGF-β2反义寡核苷酸对青光眼滤过术后结膜囊成纤维细胞的转化、增生的影响。方法制备兔青光眼滤过手术模型。右眼结膜下注射TGF-β2反义寡核苷酸(A组);左眼分别注射TGF-β2错义寡核苷酸(B组)、PBS(C组),于造模后第4、7、14、28 d取术区结膜囊标本进行免疫组织化学染色和电镜观察。结果A组眼压术后第14 d和第21 d比B组(P<0.01)和C组(P<0.05)显著降低;滤泡平均生存时间A组(17.2 d)较B组(14.5 d)、C组(13.5 d)明显延长(P<0.05);A组α-SMA和PCNA阳性成纤维细胞数明显少于B、C组;成纤维细胞的超微结构A组和B、C组比较无明显区别。结论TGF-β2反义寡核苷酸可降低兔青光眼滤过术后眼压,延长滤泡生存时间,抑制兔青光眼滤过术后结膜囊成纤维细胞的转化、增生。Objective Currently available anti-scarring regimens for glaucoma filtration surgery have potentially blinding complications and thus more attentions should be paid to the need for alternative and safer agents. This experiment was to investigate the effect of TGF-β2 antisense oligodeoxynucleotide on differentiation and proliferation of subconjunctival fibroblast following glaucoma filtration surgery. Methods Glaucoma filtration surgery were performed on both eyes of 28 rabbits. TGF-β2 antisense oligodeoxynucleotide was subconjunctivally injected in the right eyes （ A group） , and TGF-β2 missense oligodeoxynucleotide （ B group） or PBS（C group） was used at the same method in the left eyes. Rabbits were killed at 4,7,14 and 28 days after surgery. Intraocular pressure （lOP）, bleb characteristics including length, width, and height were recorded at different time point. Subconjunctival fibroblasts were examined by immunohistochemical assay and electron microscopy. Results The IOP of rabbits was significantly decreased at 14 days （6. 74 ± 1. 18 mmHg） and 21 days（8. 15 ± 1.97 mmHg） after operation in comparison with B group（8.53 ±1.04,9.72 ±1.09 mmHg） （P 〈0.01） and C group（8.79 ± 1.21,9.43 ± 1.27 mmHg） （P 〈0.05）. The mean bleb survival time was longer （ 17.2 days） in A group than B group（ 14. 5 days） and in C group （ 13.5 days） （P 〈0. 05）. The population of cells expressing smooth muscle actin（α-SMA） and proliferating cell nuclear antigen （PCNA） was significantly reduced in A group. The uhrastructure of fibroblast was not altered by TGF-β2 anti-sense oligodeoxynucleotide. Conclusion TGF-β2 antisense oligodeoxynucleotide can prevent the scar forming after glaucoma surgery by inhibiting the differentiation and proliferation of subconjunctival fibroblast. It will be a potentially useful development in the prevention of late surgical failure.

关 键 词：TGF-Β2 反义基因治疗 青光眼 瘢痕 

分 类 号：R779.6[医药卫生—眼科]