Dynamic changes of nuclear factor-kappa B expression following corneal transplantation and interventional effect of cyclosporin A

Honghua YU; Jinyin DENG; Xiaohe LU

ABSTRACT

BACKGROUND:

Nuclear factor-kappa B (NF-κB) plays a key role in regulating expressions of cytokines and adhesion factors during transcription and in central adjustment during corneal graft rejection reaction.

OBJECTIVE:

To study the dynamic expressions of NF-κB, intercellular adhesion molecular 1 (ICAM-1) and vascular endothelial growth factor (VEGF) in corneal graft and to investigate the interventional effect of cyclosporin A (CsA). DESIGN, TIME AND

SETTING:

A randomized controlled animal study was performed in the Department of Ophthalmology, Zhujiang Hospital, the First Military Medical University of Chinese PLA between January and July 2005.MATERIALS 40 SD rats and 50 Wistar rats were included and randomly divided into three groups, syngenic transplantation (10 Wistar rats used as donor and another 20 Wistar rats used as acceptor), allogeneic transplantation (10 Wistar rats used as donor, and 20 SD rats used as acceptor), and allogeneic transplantation+CsA treatment (10 Wistar rats used as donor, and 20 SD rats used as acceptor).

METHODS:

Comeal transplantation models were established. Gentamicin (2 000 U) was subconjunctivally injected into the experimental eyes of all ecceptors every other day for three times in total; chloroptic (2.5 g/L) was then used two droplets every time, twice a day, and 18 successive days in total; additionally, tropicamide (5 g/L) was also used two droplets every time, once a day, and 7 successive days in total. One day after corneal transplantation, CsA eye droplet (10 g/L) was used in the allogeneic transplantation+CsA treatment group two droplets every time, three times a day, and 18 successive days in total.MAIN OUTCOME

MEASURES:

Scores of corneal graft rejection reaction index were measured at day 3, 7, 12, and 18 after corneal transplantation; pathological changes of corneal graft were observed at the same time points to detect expressions of NF-κB, ICAM-1, and VEGF.

RESULTS:

Rejection reaction was not observed in the syngenic transplantation group at 18 days; however, indexes of rejection reaction in the allogeneic transplantation group were higher than those in the syngenic transplantation group at four time points (P<0.05), but indexes in the allogeneic transplantation+CsA treatment group were lower than those in the allogeneic transplantation group (P<0.05). Immunohistochemical examination indicated that NF-κB, ICAM-1, and VEGF were located at corneal epithelial lamina and substantia propria layer and in newborn vascular endothelial cells. At each time point, expressions of NF-κB, ICAM-1, and VEGF in the allogeneic transplantation group were higher than those in the syngenic transplantation group (P<0.05) but lower than those in the allogeneic transplantation+CsA treatment group (P<0.05).

CONCLUSION:

CsA can weaken nuclear translocation and activity of NF-κB to inhibit expressions of cytokines, adhesion molecules, and other relative factors so as to inhibit ccurrence and development of corneal graft rejection reaction.