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Expression of lysophosphatidic acid, autotaxin and acylglycerol kinase as biomarkers in diabetic retinopathy

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Abstract

The proinflammatory lysophosphatidic acid (LPA) is a potent activator of several transcriptional factors and signaling pathways and a potent modulator of genes involved in inflammation, angiogenesis and fibrosis. This study was conducted to measure the levels of LPA and LPA-producing enzymes, autotaxin (ATX) and acylglycerol kinase (AGK) in the vitreous fluid from patients with proliferative diabetic retinopathy (PDR) and to correlate their levels with clinical disease activity and the level of vascular endothelial growth factor (VEGF). In addition, we examined the expression of ATX, AGK and VEGF receptor-2 (VEGFR-2) in the retinas of diabetic rats. Vitreous samples from 42 PDR and 35 nondiabetic patients were studied by enzyme-linked immunosorbent assay. Vitreous samples and retinas of rats were examined by Western blot analysis. VEGF, LPA and AGK levels in vitreous samples from PDR patients were significantly higher than those in control patients without diabetes (p < 0.001 for all comparisons). ATX levels in PDR with active neovascularization and inactive PDR were significantly lower than those in nondiabetic patients (p = 0.045). Mean VEGF and AGK levels in PDR with active neovascularization were significantly higher than those in inactive PDR and nondiabetic patients (p < 0.001 for both comparisons). A significant correlation was observed between levels of VEGF and levels of AGK in PDR patients (r = 0.954; p < 0.001). Western blot analysis revealed a significant increase in the expression of AGK and VEGFR-2 in vitreous samples and the retinas of diabetic rats compared to nondiabetic controls, whereas ATX was significantly downregulated. Our findings suggest that ATX–AGK–LPA signaling axis might be an important player in the development and progression of diabetic retinopathy.

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Acknowledgments

The authors thank Ms. Connie B. Unisa-Marfil for secretarial work. This work was supported by Dr. Nasser Al-Rasheed Research Chair in Ophthalmology (Abu El-Asrar AM).

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None.

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Authors and Affiliations

  1. Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia

    Ahmed M. Abu El-Asrar, Ghulam Mohammad, Mohd Imtiaz Nawaz, Mohammed Miraj Siddiquei & Dustan Kangave

  2. Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium

    Ghislain Opdenakker

  3. Department of Ophthalmology, King Abdulaziz University Hospital, Old Airport Road, P.O. Box 245, Riyadh, 11411, Saudi Arabia

    Ahmed M. Abu El-Asrar

Authors
  1. Ahmed M. Abu El-Asrar
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  2. Ghulam Mohammad
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  3. Mohd Imtiaz Nawaz
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  4. Mohammed Miraj Siddiquei
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  5. Dustan Kangave
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Corresponding author

Correspondence to Ahmed M. Abu El-Asrar.

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Communicated by Renato Lauro.

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Abu El-Asrar, A.M., Mohammad, G., Nawaz, M.I. et al. Expression of lysophosphatidic acid, autotaxin and acylglycerol kinase as biomarkers in diabetic retinopathy. Acta Diabetol 50, 363–371 (2013). https://doi.org/10.1007/s00592-012-0422-1

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  • DOI: https://doi.org/10.1007/s00592-012-0422-1

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