June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Chloroquine retinopathy as a modern model of macular degeneration
Author Affiliations & Notes
  • Wennan Lu
    Anatomy & Cell Biology, Univ of Pennsylvania, Philadelphia, PA
  • Nestor Gomez
    Anatomy & Cell Biology, Univ of Pennsylvania, Philadelphia, PA
  • Jason C Lim
    Anatomy & Cell Biology, Univ of Pennsylvania, Philadelphia, PA
  • Alan M Laties
    Ophthalmology, Univ of Pennsylvania, Philadelphia, PA
  • Claire H Mitchell
    Anatomy & Cell Biology, Univ of Pennsylvania, Philadelphia, PA
    Physiology, Univ of Pennsylvania, Philadelphia, PA
  • Footnotes
    Commercial Relationships Wennan Lu, None; Nestor Gomez, None; Jason Lim, None; Alan Laties, None; Claire Mitchell, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4218. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Wennan Lu, Nestor Gomez, Jason C Lim, Alan M Laties, Claire H Mitchell; Chloroquine retinopathy as a modern model of macular degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4218.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: The lack of appropriate models for age-related macular degeneration (AMD) limits the field. Chloroquine retinopathy, also known as Bull's eye maculopathy, is associated with considerable lipid accumulations in and around RPE cells, a loss of photoreceptors and impaired vision. While the disease shares many morphological similarities with AMD, it is unknown whether chloroquine induces the biochemical or molecular markers of oxidative stress that have been linked to the disease. We have thus developed in vivo and in vitro models of chloroquine retinopathy to investigate additional parallels with AMD.

Methods: Mouse chloroquine retinopathy was induced by injecting chloroquine (50mg/kg) intraperitoneally into 3-month old C57BL/6J mice 3x/week for 6 weeks. Retinas were analyzed using protein immunoblot, ELISA, qPCR and histochemical examination. BODIPY 493/503 staining was used to evaluate accumulation of neutral lipids in Bruch's membrane. Assays were also performed on ARPE cells fed with photoreceptor outer segments (POS) and treated with chloroquine.<br />

Results: Mice treated with chloroquine showed an increase in the lipids surrounding Bruch’s membrane compared to untreated mice, an increase in SOD2 mRNA and an increase in HNE-adducted proteins in the RPE/choroid. Increased TUNEL staining was also detected in the photoreceptors of chloroquine-treated mice. The addition of chloroquine to POS-treaded ARPE cells increased the levels of retained opsin levels, consistent with impaired degradation. Levels of oxidized lipids and of HNE-adducted proteins were also increased in chloroquine treated cells.<br />

Conclusions: These data demonstrate that murine and cellular models of chloroquine retinopathy demonstrate elevations in oxidative stress markers associated with age-related macular degeneration.<br />

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×