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Development of Retinal Degeneration in Adult CCL2/CX3CR1 Deficient Mice: a Model of Age‐Related Macular Degeneration
Author(s) -
Tuo Jingsheng,
Bojanowski Christine M,
Shen Defen,
Zhou Min,
Ross Robert J,
Chan ChiChao
Publication year - 2006
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.20.5.a1324
Senescent CCL2 deficient mice develop cardinal features of age‐related macular degeneration (AMD). Variation within CX3CR1 has been associated with human AMD. We cross‐bred CCL2 and CX3CR1 knockouts mice (KO) to generate double KOs (DKO). Age‐matched wild‐type mice with similar genetic background were used as the control. Among the 400 F2 pups analyzed, 12 animals were DKOs, indicating an abnormal Mendelian segregation. DKOs showed a 20% decrease in weight and appeared to be less fertile. Forty percent DKOs showed patchy skin depigmentation. At as early as two months old, some DKOs spontaneously developed typical features of drusen‐like lesions. Histology showed retinal pigment epithelium (RPE) vacuolation and degeneration, drusen formation, photoreceptor atrophy, and a few cases of choroidal neovascularization. Complement factor deposits were detected in RPE, Bruch's membrane and choroid. Electron microscopy illustrated linear deposits within Bruch's membrane and decreased melanosomes and increased lipofusions in the RPE. These human AMD‐like morphologies progressed with age. The observations made in this study implicate the important roles of certain chemokines and possible macrophage dysfunction in AMD pathogenesis. Due to the early development of AMD features, these mice may serve as a better tool for the study of AMD and may help in the evaluation of various therapies for this blinding disease.