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H. Chen, B. Liu, T. J. Lukas, A. H. Neufeld; In Old Mice, the Retinal Pigment Epithelium/Choroid Becomes Immunologically Active. Invest. Ophthalmol. Vis. Sci. 2008;49(13):204.
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Recent studies suggest a role for the immune system in age-related macular degeneration (AMD). Our microarray analyses of retinal pigment epithelium (RPE) /choroid from normal, old mice showed intense immunological activity in old animals. To further characterize age-related changes in immune and inflammatory activities of normal, old mice, we studied expression of immunological molecules in the normal, aged RPE /choroid.
Comparing young (4 mos) and old (26 mos) mice, we determined the expression levels of genes that participate in immunological and inflammatory pathways using real-time RT-PCR, the distribution of the proteins in RPE/choroid by immunofluorescence staining and the protein levels by Western blot.
Quantitative real-time RT-PCR showed that the expression levels of selected genes from the upregulated pathways, e.g. leukocyte extravasation signaling (ICAM1, ITGB2), complement cascade (C1, C3), natural killer cell signaling (FCER1G, SH3BP2, SYK), IL-10 signaling (CCR1, IL1RN), and B cell receptor signaling (Bcl2A1, CD45), were significantly increased in the normal RPE/choroid of old animals compared to young animals. Immunofluorescence labeling showed the presence of key proteins in immunological pathways in the normal RPE/choroid of old animals. In young animals, there was little to no labeling. Western blots showed the levels of these proteins were increased in the normal RPE/choroid of old animals compared to young animals.
The present study demonstrates upregulation of gene products that participate in immune reponses and inflammatory activity in the RPE/choroid in normal, old animals. These marked changes suggest that the aged RPE/choroid had become immunologically active and might contain the underlying cellular and molecular changes that permit the development of AMD.
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