From this experiments allogenic penetrating keratoplasty rat model we find that no macroscopic NV can be found on the first three days after operation. From the forth day, conjunctiva vessels extend towards the limbus, thicken and enlarge significantly and divide into everal branches, which are significantly prominent than normal (Figure 1). CNV surround limbus like the hair of a brush at the beginning (Figure 2) then extend towards the centre of cornea gradually. They are distorted and massive vessles with branched tails (Figure 3), extend from the periphery area towards the center and invad implant finally(Figure 4). On day 8 the quantity and density of NV reach the peak, vessels cross like reticulum and spread the whole cornea (Figure 5). Then the vessles gradually atrophy to become linar lines.
From Figure 4 the CNV change with time significantly. Because of the differences in cornea radiuses, percentages that CNV accounting the whole cornea area could reflect its change tendency more objectively. On day 4 the NV accounting 31% of the whole cornea area on average, the maximum value is 67%. On day 7 the CNV reach the maximum area, which is 65.3% on average and the maximum was 97%. CNV begin to atropy on day 15, though the average percentage still is 59.5%. We could see from Figure3,4 that the total area has decreased. The NV areas decrease significantly on day 30, the average percentage is 36%, which only was a half of its peak value.
Though macroscopic CNV appear on 34 days postoperative, neoangiogenesis process starts immediately since it is triggered by wound repairing and inflammation meachanism. Antiinflammation therapy should be started as early as possible to prevent angiogenesis. Because sutures are left for a long time, the time of antiinflammation therapy should be extended as long as possible. As an important inflammation factor, IL1 could interrupt vascular endothelial cell directly,stimulate the migration and hyperplasia of them and increase the synthesis of many angiogenesis factors (VEGF,IL8,FGF,MMPs)[69]. Antiinflammation drugs such as NSAIDs had inhibitory effect on NV induced by vascular endothelial growth factor [10].
In this experiment we only observed until 30 days after operation, four observation days were settled and the spans were quit long, both of these designs would effect the accuracy of test. The formula C/12×3.14×[r2(rI)2] to calculate CNV area assumed that the NV had uniformed density [11], but in fact the density of NV varied greatly. This also maybe a factor affecting the objectivity of final results.
【参考文献】 1 Williams KA, Coster DJ.The immunobiology of corneal transplantation. Transplantation2007;84(7):806813
2 Cursiefen C, Cao J, Chen L, Liu Y, Maruyama K, Jackson D, Kruse FE, Wiegand SJ, Dana MR, Streilein JW.Inhibition of hemangiogenesis and lymphangiogenesis after normalrisk corneal transplantation by neutralizing VEGF promotes graft survival. Invest Ophthalmol Vis Sci 2004;45(8):26662673
3 Cursiefen C. Immune privilege and angiogenic privilege of the cornea. Chem Immunol Allergy2007;92:5057
4 Zhang SX, Ma JX. Ocular neovascularization:Implication of endogenous angiogenic inhibitors and potential therapy. Prog Retin Eye Res2007;26(1):137
5 ZhangY, Lu XH. Progression of corneal neovascularization mechanism and regulation. Rec Adv Ophthalmol2008;28(9):708714
6 ChévezBarrios P. Are we getting closer to prevention and treatment of corneal neovascularization? Clin Experiment Ophthalmol2007;35:689690
7 Ma DH, Chen JK, Zhang F, Lin KY, Yao JY, Yu JS. Regulation of corneal angiogenesis in limbal stem cell deficiency. Prog Retina Eye Res 2006;25(6):563590
8 Nakao S, Kuwano T, TsutsumiMiyahara C, Ueda S, Kimura YN, Hamano S, Sonoda KH, Sajio Y, Nukiwa T, Strieter RM, Ishibashi T, Kuwano M, Ono M.Infiltration of COX2expressing macrophages is a prerequisite for IL1βinduced neovascularization and tumor growth. J Clin Invest2005;115(11):29792991
9 Kuwano T, Nakao S, Yamamoto H, Tsuneyoshi M, Yamamoto T, Kuwano M, Ono M. Cyclooxygenase 2 is a key enzyme for inflammatory cytokineinduced angiogenesis. FASEB J2004;18(2):300310
10 Pakneshan P, Birsner AE, Adini I, Becker CM, DAmato RJ. Differential suppression of vascular permeability and corneal angiogenesis by nonsteroidal antiinflammatory drugs. Invest Ophthalmol Vis Sci 2008;49(9):39093913
11 DAmato RJ, Loughnan MS, Flynn E, Folkman J. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci U S A1994;91(9):40824085
上一页 [1] [2] |