Abstract
Purpose: :
Retinpathy of prematurity(ROP) is a potentially blinding condition involving pathologic neovascularization in premature babies. We have analyzed subretinal fluid (SRF) and neovascular membranes from eyes with stage 5 ROP for presence of angiogenic and immune cytokines, and for presence of macrophages, respectively. We postulate that immune cytokines and activated macrophages participate in pathogenesis of advanced ROP.
Methods: :
SRF was collected from 10 patients with advanced ROP (stages 5) and compared with SRF from patients with acute rhegmatogenous retinal detachment (RRD), a condition not associated with angiogenesis. SRF was pooled and analyzed by human cytokine antibody array and Nitric oxide assay. Immunohistochemistry (peroxidase and fluorescent) was performed on ROP (n=10) and epiretinal membranes (n=3).
Results: :
The cytokine antibody array (≥2.5 fold densitometry ROP/RRD) revealed that growth factors other than VEGF were upregulated in advanced ROP. These included angiopoietin–2, BMP–6, EGF, GM–CSF, HGF, ICAM–1, oncostatin M, PlGF, and TGF– ß1.Increased expression of macrophage modulating/ recruiting cytokines was also seen including IL–8, TGF–1ß and GM–CSF, IFN– γ, IL–1ß, TNF–α, MCP–3, and MCP–4. SRF from ROP and not RRD was able to activate macrophages in vitro. Immunohistochemistry showed the presence of activated macrophages in ROP retrolental membranes.
Conclusions: :
The proteomic differences between ROP SRF and RD SRF revealed that both angiogenic and immunogenic cytokines other than VEGF were expressed in eyes with advanced ROP. Although the source of macrophage in neovascular membranes is unknown, these macrophages may participate in the disease process.
Keywords: retinopathy of prematurity • cytokines/chemokines • neovascularization