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A.C. Lambooij, R.W. Kuijpers, D.J. Lindenbergh-Kortleve, K.H. van Wely, M.M. Kliffen, C.M. Mooy; Insulin-like Growth Factor-I and its Receptor in Neovascular Age-related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1713.
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Purpose: The insulin-like growth factor-I (IGF-I) protein is a growth promoting polypeptide that can act as an angiogenic agent in the eye. The purpose of our study is to localize the expression of IGF-I and its receptor (IGF-IR) mRNA and IGF-IR protein in situ in the normal human eye and to examine the presence of expression in eyes with neovascular age-related macular degeneration (AMD). Methods: Formalin-fixed, paraffin-embedded slides of 4 normal control eyes, 14 eyes with choroidal neovascularization (CNV) secondary to AMD were used. IGF-I and IGF-IR mRNA was detected by in-situ hybridization with digoxigenin-labeled RNA probes. IGF-IR protein was studied by immunohistochemistry. Results: In the normal retina, IGF-I and IGF-IR mRNA expression was found throughout the neuroretinal layers, in the retinal pigment epithelium (RPE) and in some choriocapillary and retinal capillary endothelial cells. In eyes with CNV we found IGF and IGF-IR mRNA in capillary endothelial cells, some transdifferentiated RPE, and fibroblast-like cells. IGF-IR protein was found in normal eyes in all neuroretinal layers, in the RPE, and in the choroidal vessels. In eyes with CNV, we found IGF-IR protein in the RPE monolayer, in transdifferentiated RPE and in newly formed vessels. Conclusions: The co-localization of protein and receptor indicates an autocrine function of IGF-I in the normal human retina. Since IGF-I participates in ocular neovascularization, synthesis of IGF-IR and IGF-I in endothelial cells, RPE cells and fibroblast-like cells in CNV may point towards a role of this growth factor in the pathogenesis of neovascular AMD.
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