September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
The aged Cxcr5 knockout mice develop the features of age-related macular degeneration
Author Affiliations & Notes
  • Hu Huang
    Ophthalmology, Johns Hopkins Wilmer Eye Inst, Baltimore, Maryland, United States
  • WEN LI
    Ophthalmology, Johns Hopkins Wilmer Eye Inst, Baltimore, Maryland, United States
    Ophthalmology, 3. Aier School of Ophthalmology, Central South University, ChangSha, Hunan, China
  • Gerard A Lutty
    Ophthalmology, Johns Hopkins Wilmer Eye Inst, Baltimore, Maryland, United States
  • Footnotes
    Commercial Relationships   Hu Huang, None; WEN LI, None; Gerard Lutty, None
  • Footnotes
    Support  Brightfocus foundation
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Hu Huang, WEN LI, Gerard A Lutty; The aged Cxcr5 knockout mice develop the features of age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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

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Abstract

Purpose : The purpose of this study is to investigate the role of the chemokine receptor Cxcr5 in the pathogenesis of age-related macular degeneration (AMD).

Methods : The 9~15-month-old Cxcr5 knockout (-/-) mice were examined for Crb1 (or rd8) gene genotype and fundus appearance. The cryopreserved and ultrathin eye sections were made for histopathological assessments using H&E staining, light and transmission electron microscopy (TEM). Retinal pigmented epithelium (RPE) flatmounts were prepared for the staining of tight junction zonula occludens (ZO)-1 and macrophage/microglia marker F4/80. Laser-induced choroidal neovascularization (CNV) areas and retinal layers were isolated by laser capture micro-dissection (LCM) for gene expression analysis.

Results : The aged Cxcr5-/- mice developed several features of age-related macular degeneration (AMD): drusen-like spots, lipofuscin and lipid deposits, RPE death, phagocytosis defect, and inflammatory cell accumulation. These AMD-like features were not caused by retinal degeneration because Cxcr5-/- mice did not have rd8 mutation in Crb1 gene. The fundus of aged Cxcr5-/- mouse had numerous white spots, which appeared to be drusen. These drusen-like spots became bigger and merged with age. Hyperpigmention, hypopigmention, and geographic atrophy were detected at the aged Cxcr5-/- mice. The protein level of tight junction ZO-1 was reduced in the RPE of aged Cxcr5-/- mice. TEM revealed the undigested photoreceptor outer segments and many vacuoles in the RPE. Additionally, F4/80 (+) microglia or macrophages accumulated in the sub-retinal space. The Cxcr5 (+) inflammatory cells migrated to the photoreceptors in the laser-induced CNV. Cxcl13, the ligand for Cxcr5, was expressed by photoreceptors and the cells of inner nuclear layer in the proximity to CNV.

Conclusions : The results suggest that Cxcl13-Cxcr5 axis plays a critical role in the pathogenesis of AMD, perhaps by controlling the migration of inflammatory cells to and/or from the RPE and photoreceptors.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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