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Suppression of retinal neovascularization by the iNOS inhibitor aminoguanidine in mice of oxygen-induced retinopathy

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Abstract

Background

Retinal neovascularization (NV) is a major cause of blindness associated with ischemic retinal disorders. Our study was focused on evaluating the inhibitory effect of aminoguanidine (AG), an inhibitor of inducible nitric oxide synthase (iNOS), on retinal NV in mice of oxygen-induced retinopathy (OIR).

Methods

An OIR model was established with 7-day-old C57BL/6J mice. One day before and 1 and 3 days after being returned to the room air, the right eyes were injected intravitreally with bevacizumab, AG or bevacizumab+AG respectively. The left eyes were injected with normal saline (NS) as control. The mice were killed at postnatal day 17 (P17). The effects of AG or bevacizumab on iNOS or VEGF expressions were evaluated by RT-PCR and immunohistochemistry. Retinal NV was examined by fluorescein angiography, and was quantified histologically by CD34 immnunostaining at P17.

Results

Compared with NS-treated eyes, retinal VEGF and iNOS mRNA expressions were significantly reduced in AG- and bevacizumab+AG-treated eyes; whereas in bevacizumab-treated eyes, retinal VEGF mRNA expression increased and iNOS mRNA expression remained unchanged. The above changes were confirmed by immunohistochemical study. The generalized decrease in both VEGF and iNOS distributions in mice retina treated with AG or bevacizumab+AG was demonstrated by immunohistochemistry. Retinal NV was significantly reduced in all three groups treated with bevacizumab, AG or bevacizumab+AG, when compared with NS-treated eyes.

Conclusions

iNOS activation plays a pathological role in retinal NV in a mouse model of ischemic retinopathy. Administration of AG significantly suppressed retinal NV. Therefore, AG appears to be a novel and effective therapeutic approach for retinal NV.

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Acknowledgement

This work was supported by the following research grants:

1. Shanghai Leading Academic Discipline Project: S30205;

2. Shanghai Public Health Bureau: 2007013;

3. Shanghai Science and Technology Committee: 08JC1415600.

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Authors and Affiliations

  1. Department of Ophthalmology, Ruijin Hospital Affiliated to Shanghai JiaoTong University School of Medicine, No 197, Ruijin Er Road, Shanghai, 200025, China

    Qiong Zhang, Shisheng Zhang, Caihong Zhu & Ling Wang

  2. Tongji Eye Institute and Department of Regenerative Medicine, Tongji University School of Medicine, 1239 Siping Road, Medical School Building, Room 521, Shanghai, 200092, China

    Jingfa Zhang & Guo-Tong Xu

  3. Laboratory of Clinical Visual Sciences, Institute of Health Sciences, Shanghai JiaoTong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China

    Yuan Guan

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  1. Qiong Zhang
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Correspondence to Guo-Tong Xu or Ling Wang.

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Ling Wang and Guo-Tong Xu are co-corresponding authors who contributed equally to this study.

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Zhang, Q., Zhang, J., Guan, Y. et al. Suppression of retinal neovascularization by the iNOS inhibitor aminoguanidine in mice of oxygen-induced retinopathy. Graefes Arch Clin Exp Ophthalmol 247, 919–927 (2009). https://doi.org/10.1007/s00417-009-1066-x

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  • DOI: https://doi.org/10.1007/s00417-009-1066-x

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