The expression of CD147, matrix metalloproteinases-2 and vascular endothelial growth factor in a rat model of oxygen induced retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

YangHuawei ,  LeiNingyu , WangLijun , 薛有余 , 张翠芳

Department of Ophthalmology, Binzhou Medical College Hospital, Binzhou 256600, China;

Corresponding author：

LeiNingyu, Email: yhwj1987@163.com

Keywords：

Retinopathy of prematurity/etiology; Antigens,CD147; Disease models,animal

DOI：

10.3760/cma.j.issn.1005-1015.2014.01.018

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Objective To observe the expression of CD147, matrix metalloproteinases-2 (MMP-2) and vascular endothelial growth factor (VEGF) in a rat model of oxygen induced retinopathy (OIR). Methods Eighty-four neonatal Wistar rats were divided into two groups randomly, the hyperoxia group (n=42) and the control group (n=42). Oxygen induced retinopathy was established in the hyperoxia group, the control group was raised in room air. Wholemonts were prepared from postnatal day (p) 7 and 14 rat retina to observe retinal vascular morphology. The number of endothelial cells to break through the internal limiting membrane was counted from p14 retinal paraffin sections. Expression of CD147, MMP-2 and VEGF protein levels was analyzed by immunohistochemistry on p12, p14, and p16 retinal sections. At the meantime, correlation between CD147 and MMP-2, VEGF was analyzed by two-way analysis of variance (ANOVA) test. Results At p7, the retinal vasculature of the control group was radial distributed with large caliber. In OIR group, there were vasoconstriction, large area of avascular zone and a few small areas of vascular network. At p14, the normal untreated rat had interwoven retinal vasculature, but in OIR group, the retinal vasculature was expanded and tortuous, and forming lots of neovascular cluster in the boundary of the perfusion and non-perfusion regions resulting exudation and hemorrhage. At p14, the endothelial cell nuclei breakthrough the internal limiting membrane was (1.30±1.26) and (19.70±3.56) respectively in control and OIR group, the difference was statistically significant (t=21.813, P<0.01). Immunohistochemical staining showed that CD147, MMP-2, VEGF expression was low in control group but high in OIR group. From p12 to p16, CD147, MMP-2 and VEGF protein expression increased in OIR retinas compared with control samples(p12:t=5.612, 4.122, 4.955; P<0.01. p14:t=11.390, 8.047, 12.176; P<0.01. p16:t=6.355, 4.422, 5.110; P<0.01). Conclusion CD147, MMP-2 and VEGF were highly expressed in the rat model of oxygen induced retinopathy.

Citation： YangHuawei, LeiNingyu, WangLijun. The expression of CD147, matrix metalloproteinases-2 and vascular endothelial growth factor in a rat model of oxygen induced retinopathy. Chinese Journal of Ocular Fundus Diseases, 2014, 30(1): 71-74. doi: 10.3760/cma.j.issn.1005-1015.2014.01.018 Copy

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14.	迟静,马晓华,毕宏生, 等. 高氧诱导SD大鼠ROP动物模型的建立[J]. 国际眼科杂志, 2011, 11:1330-1333.
15.	Akula JD, Favazza TL, Mocko JA, et al.The anatomy of the rat eye with oxygen-induced retinopathy[J].Doc Ophthalmol, 2010, 120:41-50.
16.	Rabinowitz R, Katz G, Rosner M, et al. The effect of thalidomide on neovascularization in a mouse model of retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol, 2008, 246:843-848.
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19.	Yi WH, Wei RL, Cai JP, et al. The expression and significance of VEGF and TGF-B, in orb ital cavernous hemangioma[J]. Int J Ophthalmol, 2004, 4:247-249.

1. Smith LE. IGF21 and retinopathy of prematurity in the preterm infant[J]. Biol Neonate, 2005, 88:237-244.
2. Barnett JM, Mccollum GW, Fowler JA, et al. Harmacologic and genetic manipulation of MMP-2 and -9 affects retinal neovascularization in rodent models of OIR[J].Invest Ophthalmol Vis Sci, 2007, 48:907-915.
3. Kato T, Kure T, Chang JH, et al. Diminished corneal angiogenesis ingelatinase a deficient mice[J].FEBS Lett, 2005, 508:187-190.
4. Poumaras CJ, Miller JW, Gragoudas ES, et al.Systemic hyperoxiadecreases vascular endothelial growth factor gene expression inischemic primate retina[J].Arch Ophthalmol, 2005, 115:1553-1558.
5. Tang Y, Nakada MT, Kesavan P, et al. Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases[J]. Cancer Res, 2005, 65:3193-3199.
6. Zheng HC, Takahashi H, Murai Y, et al. Upregulated EMMPR I N/CD147 might contribute to growth and angiogenesis of gastric carcinoma:a good marker for local invasion and prognosis[J]. Br J Cancer, 2006, 95:1371-1378.
7. Schmidt R, Bultmann A, Ungerer M, et al. Extracellular matrix metalloproteinase inducer regulates matrix metalloproteinase activity in cardiovascular cells:implications in acute myocardial infarction[J]. Circulation, 2006, 113:834-841.
8. Reimers N, Zafrakas K, Assmann V, et al. Expression of extracellular matrix metalloproteinase inducer on micrometastatic and primary mammary carcinoma cells[J]. Clin Cancer Res, 2004 10:3422-3428.
9. Kathryn D, Curtin, Ian A, et al. Basigin (EMMPRIN/CD147) interacts with integin to affect cellular architecture[J]. J Cell Sci, 2005, 118:2649-2660.
10. Eliason K, Osborn J, Amsel E, et al. Incidence, progression and duration of retinopathy of prematurity in Hispanics and white non-Hispanic infants[J]. J AAPOS, 2007, 11:447-451.
11. Field D, Dorling J, Manktelow B, et al. Survival of extreme premature babies in a geographically defined population:prospective cohort study of 1994-9 compared with 2000-5[J]. BMJ, 2008, 336:1221-1223.
12. Giannantonio C, Papacci P, Molle F, et al. An epidemiological analysis of retinopathy of prematurity over ten years[J]. J Pediatr Ophthalmol Strabismus, 2008, 45:162-167.
13. Lad E, Nguyen T, Morton J, et al. Retinopathy of prematurity in the United States[J]. Br J Ophthalmol, 2008, 92:320-325.
14. 迟静,马晓华,毕宏生, 等. 高氧诱导SD大鼠ROP动物模型的建立[J]. 国际眼科杂志, 2011, 11:1330-1333.
15. Akula JD, Favazza TL, Mocko JA, et al.The anatomy of the rat eye with oxygen-induced retinopathy[J].Doc Ophthalmol, 2010, 120:41-50.
16. Rabinowitz R, Katz G, Rosner M, et al. The effect of thalidomide on neovascularization in a mouse model of retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol, 2008, 246:843-848.
17. Rajap PM, Saxena P, Kaur J. Ocular angiogenesis:mechanisms and recent advances in therapy[J]. Adv Clin Chem, 2010, 50:103-121.
18. Rennel ES, Varey AH, Church ill AJ, et al. VEGF(121) b, a new member of the VEGFxxxb family of VEGF-A splice isoforms, inhibits neovascularisation and tumour growth in vivo[J]. Br J Cancer, 2009, 101:1183-1193.
19. Yi WH, Wei RL, Cai JP, et al. The expression and significance of VEGF and TGF-B, in orb ital cavernous hemangioma[J]. Int J Ophthalmol, 2004, 4:247-249.

Chinese Journal of Ocular Fundus Diseases

The expression of CD147, matrix metalloproteinases-2 and vascular endothelial growth factor in a rat model of oxygen induced retinopathy

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