Immunohistochemical localization of low density lipoprotein receptor-related protein 1 and α 2-Macroglobulin in retinal and choroidal tissue of proliferative retinopathies

• Published in: Experimental eye research Vol. 91; no. 2; pp. 264 - 272
• Main Authors: Barcelona, P.F., Luna, J.D., Chiabrando, G.A., Juarez, C.P., Bhutto, I.A., Baba, T., McLeod, D.S., Sánchez, M.C., Lutty, G.A.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 2010
• Subjects: choroid; diabetes mellitus; ischemia; LRP1; retina; sickle cell disease; α 2-Macroglobulin; choroid; LRP1; retina; diabetes mellitus; α 2-Macroglobulin; sickle cell disease; ischemia
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2010.05.017

The immunolocalization of the low density lipoprotein receptor-related protein 1 (LRP1) and its ligand α 2-Macroglobulin (α 2M) was examined in tissues from human donor eyes of normal, diabetic and sickle cell disease subjects. Streptavidin alkaline phosphatase immunohistochemistry was performed with a mouse anti-human LRP1 and rabbit anti-human α 2M antibodies. Retinal and choroidal blood vessels were labeled with mouse anti-human CD34 antibody in adjacent tissue sections. Mean scores for immunostaining from the pathological and control eyes were statistically compared. LRP1 immunoreactivity was very weak to negative in the neural retina of normal subjects except in scattered astrocytes. LRP1 expression in diabetic eyes was detected in the internal limiting membrane (ILM), astrocytes, inner photoreceptor matrix, choriocapillaris and choroidal stroma. The ligand α 2M, however, was limited mainly to blood vessel walls, some areas of the inner nuclear layer (INL), photoreceptors, RPE–Bruch’s membrane–choriocapillaris complex, intercapillary septa, and choroidal stroma. In sickle cell eyes, avascular and vascular retina as well as choroidal neovascularization (CNV) were analyzed. In avascular areas, LRP1 immunoreactivity was in innermost retina (presumably ILM, astrocytes, and Muller cells) and INL as well as RPE–Bruch’s membrane–choriocapillaris complex and choroidal stroma. α 2M was very weak in avascular peripheral retina compared to vascularized areas and limited to stroma in choroid. In contrast, in areas with CNV, LRP1 immunoreactivity was significantly decreased in overlying retina and in RPE–Bruch’s membrane and choroidal stroma compared to the controls, while α 2M was elevated in RPE–Bruch’s membrane near CNV compared to normal areas in sickle cell choroid. The mean scores revealed that LRP1 and α 2M in neural retina were significantly elevated in astrocytes and ILM in diabetic eyes ( p ≤ 0.05), whereas in sickle cell eyes scores were elevated in ILM and INL ( p ≤ 0.05). In addition, α 2M immunoreactivity was in photoreceptors in both ischemic retinopathies. In choroid, the patterns of LRP1 and α 2M expression were different and not coincident. This is the first demonstration of the presence of LRP1 and α 2M in human proliferative retinopathies. Elevated LRP1 expression in sickle cell neural retina and diabetic inner retina and choroid suggests that LRP1 plays an important role in ischemic neovascular diseases.