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Updated: May 16, 2026
Mouse Eye Enucleation for Remote High-throughput Phenotyping
Published on: November 19, 2011
Controversial view of a genetically altered mouse model of focal retinal degeneration
Xi K Chu1, Yujuan Wang, Daniel Ardeljan
1Immunopathology Section, Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Abstract:
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.
Insights
Tumor necrosis factor-inducible gene 6 (TSG-6) protein can halt retinal lesions in a mouse model. This model, despite a confounding mutation, remains valuable for testing therapies for age-related macular degeneration (AMD).
Area of Science:
- Ophthalmology
- Immunology
- Genetics
Background:
- The Ccl2 and Cx3cr1 double knockout (DKO) mouse on an rd8 background (DKO rd8) exhibits features resembling age-related macular degeneration (AMD), including photoreceptor and retinal pigmented epithelium (RPE) degeneration.
- The presence of the Crb1 (rd8) mutation complicates its use as an AMD model, leading to debate about its suitability.
- Despite the rd8 mutation, DKO rd8 mice display distinct pathologies and immune dysfunctions beyond simple Crb1-associated degeneration.
Purpose of the Study:
- To evaluate the utility of the DKO rd8 mouse model for studying AMD-like pathology and for therapeutic compound screening.
- To assess the efficacy of tumor necrosis factor-inducible gene 6 recombinant protein (TSG-6) in ameliorating retinal lesions in this model.
Main Methods:
- Utilized a DKO rd8 mouse model exhibiting focal retinal lesions, photoreceptor atrophy, RPE degeneration, elevated A2E, and complement deposition.
- Administered TSG-6 to assess its impact on retinal lesions.
- Compared pathology in DKO rd8 mice with Crb1 (rd8) mice to differentiate disease mechanisms.
Main Results:
- TSG-6 demonstrated the ability to arrest focal retinal lesions in the DKO rd8 model.
- DKO rd8 mice showed AMD-like features, including increased A2E and immune dysfunction, in addition to rd8 retinal dystrophy.
- Intervention studies showed amelioration of Ccl2/Cx3cr1-mediated lesions, confirming the model's responsiveness.
Conclusions:
- The DKO rd8 mouse model, despite the rd8 mutation, effectively recapitulates key features of AMD and is a suitable model for therapeutic screening.
- TSG-6 shows promise as a therapeutic agent for retinal degeneration characterized by inflammation.
- The model's ability to exhibit both rd8 and Ccl2/Cx3cr1-related lesions makes it valuable for studying complex retinal diseases.
