April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
The role of WNT singling activation and its blockage in the focal retinal lesion of Ccl2-/-/Cx3cr1-/- mice with and without rd8 background
Author Affiliations & Notes
  • Jingsheng Tuo
    Laboratory of Immunology, National Eye Institute/NIH, Rockville, MD
  • Yujuan Wang
    Laboratory of Immunology, National Eye Institute/NIH, Rockville, MD
  • Rui Cheng
    Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
  • Yichao Li
    Core of visual function, National Eye Institute, Bethesda, MD
  • Mei Chen
    Centre for Vision & Vascular Science, Queen's University Belfast, Belfast, United Kingdom
  • Haohua Qian
    Core of visual function, National Eye Institute, Bethesda, MD
  • Mones S Abu-Asab
    Laboratory of Immunology, National Eye Institute/NIH, Rockville, MD
  • Heping Xu
    Centre for Vision & Vascular Science, Queen's University Belfast, Belfast, United Kingdom
  • Jian-Xing Ma
    Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK
  • Chi-Chao Chan
    Laboratory of Immunology, National Eye Institute/NIH, Rockville, MD
  • Footnotes
    Commercial Relationships Jingsheng Tuo, None; Yujuan Wang, None; Rui Cheng, None; Yichao Li, None; Mei Chen, None; Haohua Qian, None; Mones Abu-Asab, None; Heping Xu, None; Jian-Xing Ma, None; Chi-Chao Chan, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 1723. doi:
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      Jingsheng Tuo, Yujuan Wang, Rui Cheng, Yichao Li, Mei Chen, Haohua Qian, Mones S Abu-Asab, Heping Xu, Jian-Xing Ma, Chi-Chao Chan; The role of WNT singling activation and its blockage in the focal retinal lesion of Ccl2-/-/Cx3cr1-/- mice with and without rd8 background. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1723.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: The canonical Wnt signaling is activated by retinal injury. Under disease conditions, the Wnt mediates inflammatory responses. Inflammation has been detected in age-related macular degeneration (AMD) retinas and Ccl2-/-/Cx3cr1-/- (DKO) mice with or without rd8 background, a model with progressive AMD-like lesions including focal photoreceptor/RPE degeneration and A2E accumulation. We evaluated the effects of Wnt-β-catenin activation and an antibody against LRP6, the co-receptor of Wnt on these two models.

Methods: anti-LRP6 antibody (2F1, 1 μl of 5 μg/μL) was intravitreally injected into the right eyes in 3 separate experiments (DKOrd8, N=35; DKO, N=10). The left eyes were injected with mouse IgG as controls. Fundoscopy was taken before injection and sequentially monthly after injection. Two months after injection, light-adapted ERG responses were recorded; then the eyes were harvested for histopathology, the determination of retinal A2E, and molecular analysis. The microarray of ocular mRNA of 92 Wnt genes was compared between the treated and the control eyes. The phosphorylated types of LRP6 and β-catenin and endogenous forms of the proteins were assayed by Western blotting.

Results: For DKOrd8 mice, the fundus showed a slower progression or alleviation of retinal lesions in the right eyes as compared to the left eyes. Among 35 pairs of eyes, 26 (74.3%) were improved, 7 (20%) stayed the same and 2 (5.7%) remained progressing. Histology confirmed the clinical observation. Light-adapted ERG of the treated eyes exhibited larger amplitudes compared to control eyes (n=6), with greater improvements under UV light stimulus. There was a significantly lower A2E in the treated eyes compared to controls. Microarray of 92 Wnt genes expression pattern was similar in both eyes. Western blotting indicated local administration of 2F1 antibody to suppress the activation of Wnt pathway in the retina. For DKO mice, the treatment improved ERG but less effect on RPE degeneration.

Conclusions: The canonical Wnt signaling plays a role in the focal retina lesion of both DKOrd8 and DKO mice; and intravitreal anti-LRP6 antibody might be neuroprotective via deactivation of canonical Wnt pathway.

Keywords: 688 retina • 715 signal transduction: pharmacology/physiology • 637 pathology: experimental  
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