April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Aldose Reductase Deficiency Reduces Retinal Injury In The Mouse Oxygen-Induced Retinopathy Model
Author Affiliations & Notes
  • Amy C. Lo
    Eye Institute,
    Research Centre of Heart, Brain, Hormone & Healthy Aging,
    University of Hong Kong, Hong Kong, Hong Kong
  • Zhong-Jie Fu
    Eye Institute,
    University of Hong Kong, Hong Kong, Hong Kong
  • Suk-Yee Li
    Eye Institute,
    University of Hong Kong, Hong Kong, Hong Kong
  • David Wong
    Eye Institute,
    Research Centre of Heart, Brain, Hormone & Healthy Aging,
    University of Hong Kong, Hong Kong, Hong Kong
  • Sookja K. Chung
    Research Centre of Heart, Brain, Hormone & Healthy Aging,
    Anatomy,
    University of Hong Kong, Hong Kong, Hong Kong
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 3985. doi:
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      Amy C. Lo, Zhong-Jie Fu, Suk-Yee Li, David Wong, Sookja K. Chung; Aldose Reductase Deficiency Reduces Retinal Injury In The Mouse Oxygen-Induced Retinopathy Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3985.

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

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Abstract

Purpose: : Retinopathy of prematurity (ROP) is a common retinal disease in preterm infants, causing childhood blindness. The lack of pharmacological treatment for ROP creates a great need for effective and safe therapies in the fragile developing preterm infants. ROP is thought to be associated with oxidative stress due to the immature antioxidant system in preterm infants. We previously showed that genetic deletion or pharmacological inhibition of aldose reductase (AR), a rate limiting enzyme in the polyol pathway, prevented retinal ganglion cell loss and oxidative stress after retinal ischemia/reperfusion injury. Here, we assessed the effects of AR deletion on retinal injury induced by oxygen-induced retinopathy (OIR), a mouse model of ROP.

Methods: : Seven-day-old pups were exposed to 75% oxygen for five days and returned to room air for another five days. The vascular, neuronal and glial changes after OIR were compared between C57Bl/6 wild-type (WT) and AR-deficient mouse retinae. Immunohistochemistry for immunoglobulin G (IgG), PKCα, calretinin, glial fibrillary acidic protein (GFAP), nitrotyrosine (NT), and poly(ADP-ribose) (PAR) as well as Western blotting for VEGF, pho-Erk, pho-Akt, and pho-IΚB were performed.

Results: : At P12 and P17, AR-deficient mice displayed a significantly smaller central retinal vaso-obliterated area. The number of leaky blood vessels displaying IgG extravasation along GCL after OIR was significantly reduced in AR-deficient retinae. In addition, there was absence of calretinin staining for amacrine cells in INL together with seriously distorted strata in IPL of WT but not AR-deficient retinae after OIR. Meanwhile, increased GFAP staining was observed in the central-middle retinae in WT but not AR-deficient mice. Moreover, increased NT immunoreactivity in INL and PAR nuclear translocation along GCL was observed in WT retinae but these changes were not apparent in AR-deficient retinae. Induced expression of VEGF, pho-Erk and pho-Akt (involved in endothelial cell proliferation and migration) as well as pho-IΚB (related to inflammation) was observed in WT retinae but was significantly reduced in AR-deficient retinae after OIR.

Conclusions: : Our findings indicated that genetic deletion of AR protected the neonatal mouse retina against oxygen-induced retinopathy by reducing retinal avascularity, neuronal loss and oxidative stress, suggesting that AR may be a potential therapeutic target in ROP.

Keywords: retinal neovascularization • retinal glia • neuroprotection 
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