[Effects of 1alpha, 25-dihydroxyvitamin D3 on the acute immune rejection and corneal neovascularization in high-risk penetrating keratoplasty in rats].
OBJECTIVE
To investigate the effects of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), a hormone that has immunosuppressive properties, on acute rejection and corneal neovascularization in rat keratoplasty model, so as to assess the therapeutic effects and explore the mechanism of 1,25(OH)(2)D(3) as an immunosuppressant in corneal transplantation.


METHODS
High risk corneal transplantation was performed orthotopically in SD rat models of high risk penetrating keratoplasty established by placing three 10-0 nylon sutures in the central corneas for two weeks, with the Wistar rats as the donors. The SD rat models were randomly assigned into 5 groups and treated with 1,25(OH)(2)D(3) at varied concentrations and cyclosporine A (CsA). The expressions of interleukin (IL)-1alpha, tumor necrosis factor (TNF)-alpha, and vascular endothelial growth factor (VEGF) mRNA were detected by in situ hybridization (ISH).


RESULTS
1,25(OH)(2)D(3) significantly suppressed acute graft rejection and inhibited corneal neovascularization as compared with saline. 1,25(OH)(2)D(3) showed better immunomodulatory effects when administered along with CsA in rat corneal allotransplants. ISH study demonstrated that 1,25(OH)(2)D(3) strongly suppressed mRNA and protein expressions of the cytokines IL-1alpha and TNF-but not those of VEGF.


CONCLUSIONS
Topical administration of 1,25(OH)(2)D(3) can be effective in suppressing acute corneal graft rejection by inhibiting the expression of proinflammatory cytokines (IL-1alpha and TNF-alpha).
Department of Ophthalmology, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, China. luo_yue@ynmail.com
Sen-Tao
ST
Dang
Xiao-He
XH
Lu
Jin
J
Zhou
Lang
L
Bai
D000818:Animals; D016510:Corneal Neovascularization / Q000473:pathology / Q000517:prevention & control*; D006084:Graft Rejection / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015948:Keratoplasty, Penetrating / Q000276:immunology*; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D007166:Immunosuppressive Agents; D007375:Interleukin-1; D009883:Ophthalmic Solutions; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C118756:dihydroxy-vitamin D3; D014807:Vitamin D