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P. F. Barcelona, J. D. Luna, G. A. Chiabrando, C. P. Juarez, I. Bhutto, D. S. McLeod, M. C. Sanchez, G. A. Lutty; Expression and Localization of Low Density Lipoprotein Receptor-Related Protein 1 (LRP1) and 2-Macroglobulin (2M) in Retinal and Choroidal Tissue of Proliferative Retinopathies. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2945. doi: https://doi.org/.
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To determine the expression and localization of LRP1 and its ligand, 2M, in sections of eyes with proliferative diabetic (PDR) and sickle cell (SC) retinopathy.
Cryopreserved tissues from eyes of normal, PDR and SC subjects were serial sectioned. APase IHC was performed with anti-LRP1 and anti-2M antibodies. Retinal and choroidal blood vessels were identified with anti CD-34 antibody in adjacent tissue sections. Mean scores from the pathological and normal eyes were statistically compared. Confocal microscopy was done to analyze LRP1 and GFAP localization.
LRP1 was absent in the neural retina (NR) of normal subjects. LRP1 expression in PDR was detected in ILM and in some areas of choroid, whereas 2M staining was limited mainly to vessel wall, INL, RPE-Bruch’s membrane-choriocapillaris complex (CC) and choroidal stroma. In SC eyes, LRP1 in avascular (AV) area showed immunoreactivity in ILM and INL as well as RPE-Bruch’s membrane-CC and choroidal stroma. In choroidal neovascularization (CNV) area, LRP1 staining was significantly decreased in NR, RPE-Bruch’s membrane, and choroidal stroma. In AV area, 2M was limited to choroidal stroma whereas in CNV area it was in RPE-Bruch’s membrane and in choroidal stroma. The microdensitometric analysis, revealed that in NR the immunostaining of both antibodies was significantly elevated (p ≤ 0.05) in astrocytes and ILM in PDR, whereas in SC was significantly elevated in ILM and INL (p ≤ 0.05). In choroid, the pattern of LRP1 and 2M expression was not coincident. By confocal microscopy we determined that the LRP1 expression in NR of SC eyes was localized in GFAP-positive Müller cells.
This is the first demonstration of the localization of LRP1 and 2M in human proliferative retinopathies. The highest LRP1 expression in NR of SC eyes suggests that LRP1 plays an important role in neovascular diseases associated with ischemia.
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