Nylon suture induced corneal neovascularization:Postoperative dynamic changes of nuclear factor-kappa B expression

Honghua YU; Jinyin DENG; Xiaohe LU

ABSTRACT

BACKGROUND:

Corneal neovascularization not only seriously affects vision, it is also a high-risk factor for the rejection after allogeneic ceratoplasty, thus it is always a hot issue and in ophthalmology to investigate the pathogenesis of corneal neovascularization and the inhibitors for blocking its formation.

OBJECTIVE:

To induce model of corneal neovascularization in rats using nylon suture, and investigate the mechanism of nuclear factor-кB (NF-кB) in the occurrence and development of corneal neovascularization using dexamethasone as the glucocorticoid inhibitor for corneal neovascularization.

DESIGN:

A randomized controlled trial.

SETTING:

Department of Ophthalmology, Zhujiang Hospital of Southern Medical University.MATERIALS The experiments were carried out in the Zhujiang Hospital of Southern Medical University from January to April 2005. Fifty-five healthy male Wistar rats of clean degree were used. Rabbit-anti-rat NF-кB P65 monoclonal antibody, rabbit-anti-rat vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1)monoclonal antibodies, and 3,3-diaminobenzidine (DAB) kit were purchased from Wuhan Boster Biological Technology Co., Ltd.

METHODS:

①

Interventions:

The rats were randomly divided in the saline control group (n =25), dexamethasone group(n =25) and normal comea group (n =5). Corneal neovascularization using nylon suture was induced in rats in the saline control group and dexamethasone group, and then saline and dexamethasone was dropped to the right eye of the rats respectively, 2 drops for each time, 3 times a day for 18 days. Not any treatment was given to the rats in the normal cornea group. ② Evaluations The score of corneal neovascularization was evaluated in the saline control group and dexamethasone group at 1, 3, 7, 12 and 18 days postoperatively. Corneal sections were prepared to observe the histological changes of cornea under light microscope; The expressions of NF-кB, VEGF and ICAM-1 were detected with immunohistochemical staining.MAIN OUTCOME

MEASURES:

① Score of corneal neovascularization; ② Histological changes of cornea; ③ Expressions of NF-кB, VEGF and ICAM-1 in cornea.

RESULTS:

① Score of corneal neovascularization The corneal neovascularization was obviously inhibited, and scores of corneal neovascularization at different time points were all significantly lower than those in the saline control group (P ＜0.05-0.01). ② Histological changes of cornea In the dexamethasone group, corneal neuvascularization and the infiltration of inflammatory cells after suture were obviously alleviated as compared with those in the control group, and the corneal structures in each layer were relatively complete. ③ Expressions of NF-кB, VEGF and ICAM-1 in cornea In the dexamethasone group, the expressions of NF-кB, VEGF and ICAM-1 at each time points were all lower than those in the saline control group (P ＜ 0.05). The intensity of the expression of NF-кB was positively correlated with the score of corneal neovascularization and the expressions of ICAM-1 and VEGF (r =0.961, 0.922, 0.958, P ＜ 0.01).

CONCLUSION:

NF-кB is involved in the formation of corneal neovascularization possibly through upregulating the expressions of its downstream genes (VEGF, ICAM-1). Dexamethasone can inhibit the expressions of many factors related to corneal neovascularization regulated by NF-кB, including cytokines and adhesion molecules, through reducing the activity of NF-кB, and then suppresses the occurrence and development of corneal neovascularization.