June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Photoreceptors are a main generator of superoxide in retinas of diabetic mice
Author Affiliations & Notes
  • Timothy Kern
    Medicine, Case Western Reserve University, Cleveland, OH
    Stokes Veterans Administration Hospital, Cleveland, OH
  • Yunpeng Du
    Medicine, Case Western Reserve University, Cleveland, OH
  • Krzysztof Palczewski
    Pharmacology, Case Western Reserve University, Cleveland, OH
  • Bruce Berkowitz
    Anatomy/Cell Biol, Wayne State Univ Sch of Med, Detroit, MI
  • Footnotes
    Commercial Relationships Timothy Kern, Bausch & Lomb (F), PamLab (F); Yunpeng Du, None; Krzysztof Palczewski, QLT Inc (F), Polgenix Inc (E), Visum Inc (P), Amegen Inc (F); Bruce Berkowitz, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 281. doi:
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      Timothy Kern, Yunpeng Du, Krzysztof Palczewski, Bruce Berkowitz; Photoreceptors are a main generator of superoxide in retinas of diabetic mice. Invest. Ophthalmol. Vis. Sci. 2013;54(15):281.

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

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Purpose: Prior work by us and others has provided strong evidence that oxidative stress and inflammatory processes play important roles in the development of the vascular lesions of early diabetic retinopathy. Oxidative stress is known to regulate expression of pro-inflammatory proteins, thus making it important to understand the source of the oxidative stress. We have investigated the contribution of photoreceptors to the retinal oxidative stress and induction of proinflammatory ICAM-1 in diabetes.

Methods: Retinal oxidative stress was assessed histologically using dichlorofluorescein staining, and quantitatively using luciginen luminescence in C57Bl/6J mice (nondiabetic and diabetic for 2 mos). Two models that caused degeneration of photoreceptors (a genetic model (rhodopsin knockout) and a chemically-induced degeneration of photoreceptors (iodoacetic acid)) were studied after 2 mos diabetes.

Results: In the diabetic mice, dichlorofluorescein stain indicated that the majority of oxidative stress was localized in the photoreceptor layer. Both models of photoreceptor degeneration resulted in essentially total obliteration of photoreceptors. The diabetes-induced increase in superoxide observed in wildtype C57Bl/6J mice was significantly inhibited in both of the diabetic models lacking photoreceptors. The diabetes-induced induction of ICAM-1 (used as a marker of inflammation) was significantly inhibited in diabetic animals missing photoreceptors (rhodopsin knockout).

Conclusions: These findings demonstrate a critical role of photoreceptors in the diabetes-induced oxidative stress in the retina, and presumably in the pathogenesis of other lesions of diabetic retinopathy.

Keywords: 499 diabetic retinopathy • 648 photoreceptors • 634 oxidation/oxidative or free radical damage  

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