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M.N. Mehta, T. Hirose, C. Lau, A.W. Taylor, K. Lashkari; Analysis of Angiogenic Factors and Inflammatory Cytokines in Subretinal Fluid From Eyes With Advanced Retinopathy of Prematurity . Invest. Ophthalmol. Vis. Sci. 2005;46(13):4119.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Advanced ROP (stage 5) is characterized by intense retinal neovascularization leading to development of a retrolental fibrovascular membrane leading to retinal detachment and collection of subretinal fluid (SRF). We analyzed the protein composition of SRF from ROP and compared it with SRF from retinal detachment. Methods: SRF was collected from 10 patients with advanced ROP (stages 4 and 5) and compared with SRF from patients with rhegmatogenous retinal detachment (RRD). Three–dimensional fibrinogen gels were used to evaluate for pro– and anti–angiogenic activity as demonstrated by capillary tube formation using human dermal microvascular endothelial cells. Protein equilibrated fractions of SRF were pooled and subjected to cytokine antibody arrays analysis for presence of angiogenic factors and inflammatory cytokines. Results: SRF from ROP exhibited concentration–dependent pro–angiogenic response as demonstrated by increased capillary tube formation. This response was more robust than for VEGF (10 ng/ml)–induced capillary formation. In contrast, SRF from RRD fluid significantly reduced tube formation in a concentration–dependent manner. Human cytokine antibody array analysis of SRF indicated that numerous angiogenic factors including VEGF, HGF, FGFs and angiopoietin–2 were upregulated in ROP. Cytokine analysis also indicated an upregulation of immune regulatory proteins especially for macrophage activation. Conclusions: Protein analysis of SRF suggests that advanced ROP has a complicated pathophysiology which can not be explained only on basis of increased production of pro–angiogenic factors. Immune regulators especially alternative pathways for macrophage activation also seem to participate in this process.
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