期刊
BIOENGINEERED
卷 4, 期 3, 页码 130-135出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/bioe.22949
关键词
age-related macular degeneration; TSG-6; Ccl2; Cx3cr1; rd8; animal model
资金
- NEI
Tuo et al. (2012) demonstrated tumor necrosis factor-inducible gene 6 recombinant protein (TSG-6) arrest of focal retinal lesions on a Ccl2 and Cx3cr1 double deficient mouse (DKO) on rd8 background (hereon referred to as DKO rd8). DKO rd8, a model of focal retinal degeneration with earlier onset and higher penetrance than Ccl2 and Cx3cr1 single knockout strains, demonstrates characteristic features of AMD such as focal photoreceptor atrophy, retinal pigmented epithelium (RPE) degeneration, elevated ocular A2E levels and complement deposition in addition to retinal dystrophy. The discovery of the accidently introduced Crb1 mutation (rd8) in the C57BL/6N strain has led to the recent opinion that DKO rd8 is not a model of AMD but solely a model of Crb1-associated retinal degeneration. Differences between DKO rd8 and Crb1(rd8) photoreceptor and RPE pathology, as well as increased A2E and immune dysfunction, show that DKO rd8 recapitulates some AMD-like features in addition to rd8 retinal dystrophy. The appearance of rd8 lesions and Ccl2/Cx3cr1 lesions and the amelioration of most Ccl2/Cx3cr1 lesions in intervention studies show DKO rd8 to be a useful and appropriate model for therapeutic compound screening, such as the case with anti-inflammatory TSG-6.
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