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Protection of exendin-4 analogue in early experimental diabetic retinopathy

  • Neuro-ophthalmology
  • Published:
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Abstract

Background

Diabetic retinopathy (DR) is one of the leading causes of blindness, affecting over 90% of diabetics. Exendin-4 (E4) is a potent and long-acting agonist of the glucagon-like peptide-1 (GLP-1) receptor. GLP-1 is an insulinotropic gut peptide, which normalizes blood glucose level and is now being tested in clinical trials as a treatment for diabetes. The purpose of our study was to explore the protective effect of subcutaneous (sc.) exendin-4 analogue (E4a) on early DR.

Methods

Expression of GLP-1R was detected at both mRNA and protein levels and verified by immunohistochemistry. Thirty-six Sprague–Dawley (SD) rats were included in the experiment. Diabetes was induced by intraperitoneal injection (ip) of streptozotocin (STZ). The rats were divided into three groups: normal control (N), diabetic control (D) and E4a-treated diabetic (E4a) group. For the E4a group, the rats were treated with E4a (sc.0.05 μg/g BW/day); for the N and D groups, the rats were treated with normal saline (NS, sc). Blood glucose levels and body weight were measured weekly. Electroretinogram (ERG) was performed 1 and 3 months after diabetes onset. The retinal thickness and cell counts in each layer were evaluated under light microscopy after ERG examination.

Results

GLP-1R was expressed at both mRNA and protein levels in the retina of SD rats. Immunostaining of the rat retina revealed that GLP-1R was predominantly expressed in the inner layer of the retina. E4a can reduce the blood glucose level of diabetic rats to the normal control level. B-wave amplitudes and OPs decreased with the progress of diabetes, and E4a prevents the loss of b-wave amplitude and OPs caused by diabetes. The retinal thickness was reduced in a diabetes-duration-dependent fashion. The cell counts of both ONL and INL were reduced accordingly in the diabetic rats. E4a prevented cell loss and maintained a normal thickness.

Conclusions

GLP-1R is expressed in rat retina. Apoptosis is an important constituent of retinal cell death in early DR. E4a administration can reverse the changes of ERG, prevent the retinal cell death and maintain normal retinal thickness in diabetic rats. Therefore, this is a potent approach for treatment of early DR.

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Authors and Affiliations

  1. Department of Ophthalmology, Huashan Hospital Affiliated to Fudan University, 12 Middle Wulumuqi Road, Building 3, Room 802, Shanghai, 200040, China

    Yu Zhang, Qingping Wang & Wen Ye

  2. Laboratory of Clinical Visual Sciences, Institute of Health Sciences (IHS), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS) and Shanghai Jiaotong University School of Medicine (SJTUSM), 225 South Chongqing Road, Building 1, Room 712, Shanghai, 200025, China

    Jingfa Zhang, Xia Lei & Guo-Tong Xu

  3. Tongji Eye Institute, and Department of Regenerative Medicine, Tongji University School of Medicine, 1239 Siping Road, Medical School Building, Room 512, Shanghai, 200092, China

    Jingfa Zhang & Guo-Tong Xu

Authors
  1. Yu Zhang
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  2. Qingping Wang
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  3. Jingfa Zhang
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  4. Xia Lei
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Correspondence to Guo-Tong Xu or Wen Ye.

Additional information

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

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Zhang, Y., Wang, Q., Zhang, J. et al. Protection of exendin-4 analogue in early experimental diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol 247, 699–706 (2009). https://doi.org/10.1007/s00417-008-1004-3

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  • DOI: https://doi.org/10.1007/s00417-008-1004-3

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