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Aberrant endoplasmic reticulum proteins in Ccl2/Cx3cr1 deficient mice with retinal lesions mimicking human age‐related macular degeneration
Author(s) -
Tuo Jingsheng,
Rosenberg Kevin I,
Zhou Min,
Shen Defen,
Ross Robert J,
Fariss Robert N,
Yin Chunyue,
Zhuang Zhengping,
Chan ChiChao
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.a1130-b
We developed an Age‐related macular degeneration (AMD) model, Ccl2/Cx3cr1 deficient mouse, which displays AMD‐like lesions including drusen formation, retinal pigment epithelium (RPE) hypopigmentation and accumulation of lipofuscin, photoreceptor degeneration, and choroidal neovascularization. This study aimed to detect causal factors directly contributing to the phenotype of this model. The proteomics showed that 4 proteins were differentially expressed in the retina of Ccl2−/−/Cx3cr1−/−. Mass spectrophotometer confirmed that two of them were ERp29 precursor and CBP140, proteins from endoplasmic reticulum (ER). RT‐PCR, Western Blotting and immunochemistry indicated that ERp29 and CBP140 significantly down‐regulated in the retina of Ccl2−/−/Cx3cr1−/− in comparison with the wild type. Our data identified at least 2 ER proteins that are associated with an AMD‐like phenotype in Ccl2−/−/Cx3cr1−/−. ER proteins function as chaperone in protein folding and maturation. Improper function of ER leads to the accumulation of unfolded protein, which is believed to be the machismo of several age‐related or neurodegenerative diseases including AMD. ERp29 is one such ER‐resident chaperone. We expect that the ER and ER‐related proteins might play a role in the retinal phenotype of Ccl2−/−/Cx3cr1−/−. Supported by NEI intramural research program.