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Altered Erp29 and Htra1 in cultured retinal pigment epithelial (RPE) cells of Ccl2/Cx3cr1 deficient mice – a model of age‐related macular degeneration
Author(s) -
Verma Varun,
Shen Defen,
Zhang Congxiao,
Zhou Min,
Chan ChiChao,
Tuo Jingsheng
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a763
Subject(s) - cx3cr1 , macular degeneration , retinal pigment epithelium , ccl2 , biology , phenotype , endoplasmic reticulum , chemokine , retinal , retinal degeneration , microbiology and biotechnology , immunology , gene , medicine , inflammation , genetics , biochemistry , chemokine receptor , ophthalmology
Age‐related macular degeneration (AMD) is the leading cause of vision loss in the developed world. The pathogenesis involves damage to central photoreceptors, retinal pigment epithelium (RPE), Bruch’s membrane, and choriocapillaries. We developed a Ccl2/Cx3cr1 deficient mouse model with early onset AMD pathology, high penetrance and reproducibility. Erp29 is an endoplasmic reticulum protein that functions as an escort chaperone and in protein folding. Proteomics data in our lab indicated that Erp29 precursor was differentially expressed in Ccl2/Cx3cr1 deficient retinas compared to controls. Given the critical role of the RPE in AMD, we aim to evaluate Erp29 in cultured RPE cells of Ccl2/Cx3cr1 deficient mice. The Htra1 gene encodes a secreted serine protease. Recent human studies revealed that a risk allele was associated with elevated RPE expression of HTRA1. We hypothesized such an elevation in our model. RPE cells were isolated and cultured from 16‐month old mice before mRNA isolation and real‐time RT PCR. The average Erp29 level in RPE of Ccl2/Cx3cr1 deficient mice was 0.79‐fold that of the wild‐type. The low Erp29 may explain AMD pathology resulting from accumulation of unfolded protein in the affected RPE. The average Htra1 in the Ccl2/Cx3cr1 deficient mice was 2.08‐fold that of wild‐type, suggesting that Htra1 may be involved in the AMD phenotype of this model. Supported by NEI intramural research program.