Quantitative analysis of vascular endothelial growth factor and pigment epithelium-derived factor in aqueous humor before and after intravitreal injection of ranibizumab in proliferative diabetic retinopathy_Chinese Journal of Ocular Fundus Diseases

Authors：

ChenXiaohong ,  ChenMeizhu , WangYunpeng

Department of Ophthalmology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou 350025, China;

Corresponding author：

ChenMeizhu, Email: jumychen@tom.com

Keywords：

Diabetic retinopathy/drug therapy; Angiogenesis inhibitors/therapeutic use; Antibodies, monoclonal/therapeutic use; Vascular endothelial growth factors

DOI：

10.3760/cma.j.issn.1005-1015.2015.06.012

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Objective To analyze the concentrations of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in aqueous humor of patients with proliferative diabetic retinopathy (PDR) before and after intravitreal injection of ranibizumab. Methods Twenty-five eyes of 20 PDR patients were collected as the PDR group. Twenty-five eyes of 21 senile cataract patients were collected as the control group. There were no statistical significance in gender (χ²=0.223), age (Z=-1.555) and intraocular pressure (Z=-0.225) between the two groups (P > 0.05). Samples of aqueous humor (0.1 ml) were collected just before and 7 days after the injection of ranibizumab in PDR group. Samples of aqueous (0.1 ml) humor were collected just before cataract surgery in control group. The concentrations of VEGF and PEDF in the aqueous humor were measured by enzyme-linked immunosorbent assay. Results The VEGF and PEDF concentration in the aqueous humor were reduced significantly after intravitreal injection of ranibizumab in PDR group (Z=-4.072, -4.319; P < 0.05). The concentrations of VEGF and PEDF in the aqueous humor before intravitreal injection of ranibizumab in PDR group were significantly higher than the control group (Z=-5.228, 4.706; P < 0.05). The VEGF concentration in the aqueous humor after intravitreal injection of ranibizumab in PDR group were similar to control group (Z=-1.557, P > 0.05). However, the concentration of PEDF in the aqueous humor after intravitreal injection of ranibizumab in PDR group still higher than control group (Z=-2.475, P < 0.05). The ratio of VEGF/PEDF before and after intravitreal injection of ranibizumab was statistically different (Z=-2.058, P < 0.05), but was the same between PDR group and control group (Z=-0.456, -0.844; P > 0.05). The aqueous humor concentrations of VEGF and PEDF were not significantly correlated with each other, neither in PDR group (r=-0.195, -0.174; P > 0.05) nor in control group (r=-0.286, P > 0.05). Conclusions Aqueous humor concentrations of VEGF and PEDF are significantly elevated in eyes with PDR. Intravitreal injection of ranibizumab significantly decreased the VEGF and PEDF in the aqueous humor after 7 days.

Citation： ChenXiaohong, ChenMeizhu, WangYunpeng. Quantitative analysis of vascular endothelial growth factor and pigment epithelium-derived factor in aqueous humor before and after intravitreal injection of ranibizumab in proliferative diabetic retinopathy. Chinese Journal of Ocular Fundus Diseases, 2015, 31(6): 560-563. doi: 10.3760/cma.j.issn.1005-1015.2015.06.012 Copy

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7.	吕文山, 董砚虎, 钱荣立.糖尿病的诊断和分型[J].中国糖尿病杂志, 2000(1): 57, 59-60.
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13.	Wang JW, Zhou MW, Zhang X, et al. Short-term effect of intravitreal ranibizumab on intraocular concentrations of vascular endothelial growth factor-A and pigment epithelium-derived factor in neovascular glaucoma[J]. Clin Experiment Ophthalmol, 2015, 43(5):415-421.
14.	Ohno-matsui K, Yoshida T, Uetama T, et al. Vascular endothelial growth factor upregulates pigment epithelium-derived factor expression via VEGFR-1 in human retinal pigment epithelial cells[J]. Biochem Biophys Res Commun, 2003, 303(3): 962-967.
15.	Angayarkanni N, Selvi R, Pukhraj R, et al. Ratio of the vitreous vascular endothelial growth factor and pigment epithelial-derived factor in Eales disease[J]. J Ocul Biol Dis Infor, 2009, 2(1): 20-28.

1. Ng EW, Adamis AP. Anti-VEGF aptamer (pegaptanib) therapy for ocular vascular diseases[J]. Ann N Y Acad Sci, 2006, 1082: 151-171.
2. Unterlauft JD, Claudepierre T, Schmidt M, et al. Enhanced survival of retinal ganglion cells is mediated by Müller glial cell-derived PEDF[J]. Exp Eye Res, 2014, 127: 206-214.
3. Elahy M, Baindur-hudson S, Cruzat VF, et al. Mechanisms of PEDF-mediated protection against reactive oxygen species damage in diabetic retinopathy and neuropathy[J]. J Endocrinol, 2014, 222(3): 129-139.
4. Ogata N, Nishikawa M, Nishimura T, et al. Unbalanced vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor in diabetic retinopathy[J]. Am J Ophthalmol, 2002, 134(3): 348-353.
5. Matsuoka MM, Ogata NN, Minamino KK, et al. Expression of pigment epithelium-derived factor and vascular endothelial growth factor in fibrovascular membranes from patients with proliferative diabetic retinopathy[J]. Jpn J Ophthalmol, 2006, 50(2): 116-120.
6. Simunovic MM, Maberley DD. Anti-vascular endothelial growth factor therapy for proliferative diabetic retinopathy: a systematic review and meta-analysis[J]. Retina, 2015, 35(10): 1931-1942.
7. 吕文山, 董砚虎, 钱荣立.糖尿病的诊断和分型[J].中国糖尿病杂志, 2000(1): 57, 59-60.
8. Ahn JK, Moon HJ. Changes in aqueous vascular endothelial growth factor and pigment epithelium-derived factor after ranibizumab alone or combined with verteporfin for exudative age-related macular degeneration[J]. Am J Ophthalmol, 2009, 148(5): 718-724.
9. Gupta N, Mansoor S, Sharma A, et al. Diabetic retinopathy and VEGF[J]. Open Ophthalmol J, 2013, 7: 4-10.
10. Krohne TU, Liu Z, Holz FG, et al. Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans[J]. Am J Ophthalmol, 2012, 154(4): 682-686.
11. Funatsu H, Yamashita H, Noma H, et al. Aqueous humor levels of cytokines are related to vitreous levels and progression of diabetic retinopathy in diabetic patients[J]. Graefe's Arch Clin Exp Ophthalmol, 2005, 243(1): 3-8.
12. Matsuyama K, Ogata N, Matsuoka M, et al. Plasma levels of vascular endothelial growth factor and pigment epithelium-derived factor before and after intravitreal injection of bevacizumab[J]. Br J Ophthalmol, 2010, 94(9): 1215-1218.
13. Wang JW, Zhou MW, Zhang X, et al. Short-term effect of intravitreal ranibizumab on intraocular concentrations of vascular endothelial growth factor-A and pigment epithelium-derived factor in neovascular glaucoma[J]. Clin Experiment Ophthalmol, 2015, 43(5):415-421.
14. Ohno-matsui K, Yoshida T, Uetama T, et al. Vascular endothelial growth factor upregulates pigment epithelium-derived factor expression via VEGFR-1 in human retinal pigment epithelial cells[J]. Biochem Biophys Res Commun, 2003, 303(3): 962-967.
15. Angayarkanni N, Selvi R, Pukhraj R, et al. Ratio of the vitreous vascular endothelial growth factor and pigment epithelial-derived factor in Eales disease[J]. J Ocul Biol Dis Infor, 2009, 2(1): 20-28.

Chinese Journal of Ocular Fundus Diseases

Quantitative analysis of vascular endothelial growth factor and pigment epithelium-derived factor in aqueous humor before and after intravitreal injection of ranibizumab in proliferative diabetic retinopathy

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