Purchase this article with an account.
K. Ishibashi, K. Ishibashi, J. Tian, I. Bhutto, G. Lutty, J.T. Handa; A Survey of Advanced Glycation Endproduct Receptors Expressed by Human Retinal Pigment Epithelial Cells in situ . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1779.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Advanced Glycation Endproducts (AGEs) have been implicated in aging and age–related diseases including Age–related Macular Degeneration. The purpose of this study was to determine the expression of AGE receptors from normal and morphologically abnormal macular RPE cells from human donor globes. Methods: Macular RPE cells from 19 donor eyes (ages 43–92 years; 5 eyes with diabetes and 3 eyes with basal deposits) were laser capture microdissected. The RNA was extracted by column purification, and subjected to real time RT–PCR for AGE receptors: RAGE, AGER1–3, MSR B, and LOX–1. Statistical differences were assessed by the Students t–test. Eyes were also assessed for RAGE and AGER3 by immunohistochemistry. Results: The mRNA expression of RAGE was similar between donors >80 and <60 years old, but underexpressed compared to diabetic donors (p=0.01). The mRNA expression of AGER1 and AGER3 were underexpressed by macular RPE from donors >80 years old compared to donors <60 years old (p=0.027 and p=0.042, respectively) while the expression between normal and diabetic donors was similar. AGER2, MSRB, and LOX–1 expression showed no age–dependent expression, and was similar between normal and diabetic donors. Immunohistochemical analysis of RAGE showed preferential labeling in ganglion cells of the neurosensory retina, diffuse labeling of the RPE, and intermittent choriocapillaris labeling in normal eyes. In regions of basal deposits, prominent labeling was seen on the RPE basolateral surface adjacent to strong choriocapillaris endothelial cell labeling. AGER3 immunolabeling showed a similar pattern to RAGE. Conclusions: RAGE mRNA expression appears to be upregulated in disease (ie DM) while AGER1 and R3 expression is age–dependent. Immunohistochemical studies suggest upregulation of RAGE overlying basal deposits, which could represent early age–related disease.
This PDF is available to Subscribers Only