Abstract
BACKGROUND: Vascular endothelial growth factor (VEGF) has been shown to play a major role in intraocular neovascularisation in ischaemic retinal diseases. Subretinal neovascularisation is an important cause of central visual loss, but little is known about the role of this growth factor in its pathogenesis. The aim of this study was to investigate the possible role of VEGF in the development of subretinal neovascularisation. METHODS: Undiluted vitreous samples were obtained from patients undergoing vitrectomy for removal of non-age-related subfoveal neovascular membranes (SFNM). For comparison vitreous from patients undergoing vitrectomy for idiopathic full thickness macular holes (FTMH) and proliferative diabetic retinopathy (PDR) was used. Indirect enzyme linked immunosorbent assay (ELISA), with an antibody directed against the conserved N-terminal region of human VEGF165, was used to determine vitreous levels of VEGF. The growth factor was also localised in the vitreous of patients with SFNM by western blot analysis. RESULTS: The mean (SE) VEGF concentration in the vitreous of patients with SFNM was 27.78 (2.22) ng/ml (n = 8), FTMH was 16.62 (0.9) ng/ml (n = 18), and PDR was 37.77 (3.28) ng/ml (n = 16). The differences between the PDR group and SFNM group versus the FTMH group were both significant (p = 0.0001 and p = 0.0015) as analysed by the Wilcoxon rank sum test). CONCLUSIONS: Vitreous levels of VEGF are significantly elevated in eyes with non-age-related subretinal neovascularisation compared with eyes with FTMH but not as elevated as in PDR. This suggests that VEGF is involved in subretinal angiogenesis.
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- Adamis A. P., Miller J. W., Bernal M. T., D'Amico D. J., Folkman J., Yeo T. K., Yeo K. T. Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol. 1994 Oct 15;118(4):445–450. doi: 10.1016/s0002-9394(14)75794-0. [DOI] [PubMed] [Google Scholar]
- Adamis A. P., Shima D. T., Yeo K. T., Yeo T. K., Brown L. F., Berse B., D'Amore P. A., Folkman J. Synthesis and secretion of vascular permeability factor/vascular endothelial growth factor by human retinal pigment epithelial cells. Biochem Biophys Res Commun. 1993 Jun 15;193(2):631–638. doi: 10.1006/bbrc.1993.1671. [DOI] [PubMed] [Google Scholar]
- Aiello L. P., Avery R. L., Arrigg P. G., Keyt B. A., Jampel H. D., Shah S. T., Pasquale L. R., Thieme H., Iwamoto M. A., Park J. E. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994 Dec 1;331(22):1480–1487. doi: 10.1056/NEJM199412013312203. [DOI] [PubMed] [Google Scholar]
- Dvorak H. F., Detmar M., Claffey K. P., Nagy J. A., van de Water L., Senger D. R. Vascular permeability factor/vascular endothelial growth factor: an important mediator of angiogenesis in malignancy and inflammation. Int Arch Allergy Immunol. 1995 May-Jun;107(1-3):233–235. doi: 10.1159/000236988. [DOI] [PubMed] [Google Scholar]
- Gass J. D. Biomicroscopic and histopathologic considerations regarding the feasibility of surgical excision of subfoveal neovascular membranes. Am J Ophthalmol. 1994 Sep 15;118(3):285–298. [PubMed] [Google Scholar]
- Grossniklaus H. E., Martinez J. A., Brown V. B., Lambert H. M., Sternberg P., Jr, Capone A., Jr, Aaberg T. M., Lopez P. F. Immunohistochemical and histochemical properties of surgically excised subretinal neovascular membranes in age-related macular degeneration. Am J Ophthalmol. 1992 Oct 15;114(4):464–472. doi: 10.1016/s0002-9394(14)71859-8. [DOI] [PubMed] [Google Scholar]
- Hoshino S., Miyazawa H., Enomoto T., Hanaoka F., Kikuchi Y., Kikuchi A., Ui M. A human homologue of the yeast GST1 gene codes for a GTP-binding protein and is expressed in a proliferation-dependent manner in mammalian cells. EMBO J. 1989 Dec 1;8(12):3807–3814. doi: 10.1002/j.1460-2075.1989.tb08558.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keck P. J., Hauser S. D., Krivi G., Sanzo K., Warren T., Feder J., Connolly D. T. Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science. 1989 Dec 8;246(4935):1309–1312. doi: 10.1126/science.2479987. [DOI] [PubMed] [Google Scholar]
- Malecaze F., Clamens S., Simorre-Pinatel V., Mathis A., Chollet P., Favard C., Bayard F., Plouet J. Detection of vascular endothelial growth factor messenger RNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy. Arch Ophthalmol. 1994 Nov;112(11):1476–1482. doi: 10.1001/archopht.1994.01090230090028. [DOI] [PubMed] [Google Scholar]
- Pertovaara L., Kaipainen A., Mustonen T., Orpana A., Ferrara N., Saksela O., Alitalo K. Vascular endothelial growth factor is induced in response to transforming growth factor-beta in fibroblastic and epithelial cells. J Biol Chem. 1994 Mar 4;269(9):6271–6274. [PubMed] [Google Scholar]
- Saxe S. J., Grossniklaus H. E., Lopez P. F., Lambert H. M., Sternberg P., Jr, L'Hernault N. Ultrastructural features of surgically excised subretinal neovascular membranes in the ocular histoplasmosis syndrome. Arch Ophthalmol. 1993 Jan;111(1):88–95. doi: 10.1001/archopht.1993.01090010092033. [DOI] [PubMed] [Google Scholar]
- Senger D. R., Galli S. J., Dvorak A. M., Perruzzi C. A., Harvey V. S., Dvorak H. F. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science. 1983 Feb 25;219(4587):983–985. doi: 10.1126/science.6823562. [DOI] [PubMed] [Google Scholar]
- Senger D. R., Perruzzi C. A., Feder J., Dvorak H. F. A highly conserved vascular permeability factor secreted by a variety of human and rodent tumor cell lines. Cancer Res. 1986 Nov;46(11):5629–5632. [PubMed] [Google Scholar]
- Shweiki D., Itin A., Soffer D., Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992 Oct 29;359(6398):843–845. doi: 10.1038/359843a0. [DOI] [PubMed] [Google Scholar]