June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Photoreceptor death and RPE oxidative stress model of chloroquine retinopathy
Author Affiliations & Notes
  • Wennan Lu
    Basic and Translational Science, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Assraa Hassan Jassim
    Basic and Translational Science, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Nestor Mas Gomez
    Basic and Translational Science, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Claire H Mitchell
    Basic and Translational Science, University of Pennsylvania, Philadelphia, Pennsylvania, United States
    Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Wennan Lu, None; Assraa Jassim, None; Nestor Mas Gomez, None; Claire Mitchell, None
  • Footnotes
    Support  NIH Grants EY013434 and EY015537
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2714. doi:
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      Wennan Lu, Assraa Hassan Jassim, Nestor Mas Gomez, Claire H Mitchell; Photoreceptor death and RPE oxidative stress model of chloroquine retinopathy. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2714.

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

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Abstract

Purpose : Chloroquine has been linked to retinopathy for decades in humans, characterized by central visual loss and bull’s eye maculopathy. We have developed a mouse model of chloroquine retinopathy to identify key steps in disease progression. The association of chloroquine induced retinal toxicity with oxidative stress and lipid peroxidation of RPE cells was examined.

Methods : Chloroquine retinopathy was induced by injecting chloroquine (50mg/kg) intraperitoneally into adult C57BL/6J mice 3x/week for 6-8 weeks. Retinal and/or RPE material was analyzed by histology, TUNEL staining, protein immunoblot, ELISA, and qPCR. Electroretinography (ERG) was used to monitor retinal function. ARPE-19 cells were used for in vitro experiments.

Results : ERG analysis detected a moderate reduction in both the a-wave and b-wave, with increases in implicit time. Spider graphs indicated a corresponding loss of outer nuclear layer cells in chloroquine treated retinae. TUNEL analysis detected increased apoptotic DNA fragmentation in photoreceptor nuclei; no corresponding signal was detected in RPE cells. RPE/choroid material from chloroquine-treated mice displayed an increase in HNE-adducted proteins detected with both Elisa and immunoblots. Chloroquine treatment increased the number and size of lysosomes, the amount of mitochondrial staining and expression of mitochondrial biogenesis genes in vitro.

Conclusions : This study suggests that the loss of photoreceptors accompanying moderate chloroquine treatment is associated with lysosomal stress, mitochondrial biogenesis and oxidative stress in RPE cells. How these stresses in the RPE lead to photoreceptor death requires further investigation.

This is a 2021 ARVO Annual Meeting abstract.

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