ABSTRACT
BACKGROUND: Cervical lymph nodes are draining region of cornea. It is believed that aqueous fluid goes through a minor pathway named uveoscleral drainage, which will allow passage of antigen-presenting cells (APC) directly to the draining lymph nodes and induce allograft rejection after keratoplasty.OBJECTIVE: To explore the inhibitory effects of cervical lymphadenectomy in alkali induced high-risk corneal transplantation.DESIGN: A randomized controlled animal experiment.SETTING: State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University.MATERIALS: The experiment was performed in the State Key Laboratory of Ophthalmology (No. 2006DA105054), Zhongshan Ophthalmic Center, Sun Yat-sen University from May 2005 to February 2007. 144 male animals (1-2 months old) including 104 SD rats and 40 Wistar rats were provided by the animal experimental center of Sun Yat-sen University. Sandwich enzyme-linked immunosorbent assay (ELISA) kits for interleukin-2 (IL-2) and interferon-γ (IFN-γ) were brought from BioSource International company (USA). The animal treatment in the experiment was accorded with the statement in Association for Research in Vision and Ophthalmology (ARVO) for animals.METHODS: With the SD rats as recipients, and Wistar rats as donors, all rats were subjected to corneal allografting. The recipient rats were randomly divided into 4 groups (n=20): group A (control group) which underwent corneal transplantation; group B which was subjected to bilateral cervical lymphadenectomy; group C, corneal transplantation 21 days after the alkali burn injury; group D, cervical lymphadenectomy following group C. The immune rejection of grafts was evaluated by detecting the expression of IFN-γ and IL-2 using ELISA. The time when allograft rejection occurred was recorded and mean survival time (MST) was compared among the groups. The development of corneal inflammation and new vessels was examined by slit lamp microscope and histopathological examination.MAIN OUTCOME MEASURES: ①The development of corneal inflammation after corneal alkaline burns. ②MST of rats in each group following transplant. ③The expression of IL-2 and IFN-γ in grafts of each group. RESULTS: ①Normal rat cornea was transparent without inflammation or neovascularization. There were many inflammatory cells invading to stroma on day 3 after burn. Then, the inflammation of cornea resolved gradually 3 weeks after the burn, but corneal neovascularization reached the peak at that time. Corneal blood vessels regressed completely at the end of 8 weeks after the burn. ②The MST of group A, B, C, and D was (10.40±1.14), (46.30±9.46), (7.00±1.58), and (15.00±3.39) days, respectively. Compared with the group A, the MST of group B was significantly longer (P < 0.05), and the MST of grafts in group D was also significantly longer than group C (P < 0.05). ③The expression of IFN-γ and IL-2 proteins was absent in group B. Compared with group C, the expression of IL-2 and IFN-γ proteins in group D significantly decreased on days 3, 7, 10, and 14 after keratoplasty (P < 0.05). CONCLUSION: Cervical lymphadenectomy therapy can effectively inhibit corneal allograft rejection in normal and high-risk corneal beds after alkali burn injury.