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L. Zhao, Y. Song, Y. Liu, Y. Li, A.M. Laties, R. Wen; Subretinal Matrigel Induces Translocation of the RPE and Choroidal Neovascularization . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4152.
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A pathological feature of age–related macular degeneration (AMD) is the deposition of extracellular material between the retinal pigment epithelium (RPE) and Bruch’s membrane, described as sub–RPE deposits. Both the presence and local organization of these deposits contribute to the clinical manifestations of AMD. The hallmark of exudative AMD is the presence of choroidal neovascularization (CNV) in which new blood vessels from the choroid invade the sub–RPE deposits and the retina. At issue is whether the sub–RPE deposits and CNV are simply two independent manifestations of the same disease, or there is a causal relation between the two.
A rat model of sub–RPE deposit (induced by subretinal Matrigel) was used. Matrigel was injected into the subretinal space of adult Long Evans or Sprague–Dawley rats. Eyes were collected after injection and semi–thin sections were cut through the Matrigel injected area and examined by light microscopy. Thick vibratome sections (100 µm) were examined by fluorescence microscopy for CNV.
RPE cells started to migrate toward photoreceptors 5 days after Matrigel injection. They then formed a new layer separating Matrigel from photoreceptors. The Matrigel deposit thus becomes a sub–RPE deposit. Only those new blood vessels in a region unambiguously separate from the injection site were counted as CNV and thus solely induced by the presence of sub–RPE Matrigel deposit, to avoid misidentifying new blood vessels that might have induced by the needle injury. New blood vessels in regions free of needle injury were found in many samples collected 45 days after injection of Matrigel.
Our results highlight the importance of RPE as a barrier to CNV invasion. Migration of RPE cells dismantles the RPE–Bruch’s membrane complex. Bruch’s membrane devoid of RPE becomes vulnerable to CNV invasion. The observation that cell infiltration is common in samples with CNV is consistent with pathological findings from AMD patients and suggests a role of focal inflammation. A sub–RPE deposit may serve as a nidus for pathological reactions that lead to CNV development.
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