June 2013
Volume 54, Issue 15
ARVO Annual Meeting Abstract  |   June 2013
Glucocorticoids Inhibit p38MAPK Activation and Neuronal Apoptosis in Early Diabetic Retinopathy
Author Affiliations & Notes
  • Xinyuan Zhang
    Tongren Eye Center, Beijing Tongren Hospital, Beijing, China
  • Bob Bao
    Pathology, The University of Sydney, Sydney, NSW, Australia
  • Mark Gillies
    Ophthalmology, The University of Sydney, Sydney, NSW, Australia
  • Footnotes
    Commercial Relationships Xinyuan Zhang, None; Bob Bao, None; Mark Gillies, Novartis (R), Pfizer (R), Allergan (F), Bayer (F)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 6343. doi:
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      Xinyuan Zhang, Bob Bao, Mark Gillies; Glucocorticoids Inhibit p38MAPK Activation and Neuronal Apoptosis in Early Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6343.

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

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Purpose: Intravitreal glucocorticoids and anti-vascular endothelial growth factor (VEGF) therapies are novel strategies for the treatment of advanced diabetic retinopathy, a condition with inflammatory and neuropathic elements. In contrast with anti-VEGF therapy, glucocorticoids may also exert neuroprotective effects. How glucocorticoids protect retinal neurons is unknown. The aims of the study are to investigate the anti-apoptotic actions of glucocorticoids on diabetic retinal neurons, and characterize the signaling cascade involved.

Methods: The regulation of gene expression of the four p38 mitogen-activated protein kinase (MAPK) isoforms (α, β, δ and γ) and the glucocorticoid receptor (GR) in the retinas was evaluated, using quantitative RT-PCR, Western blot and immunohistochemistry. Phosphorylation of all isoforms p38MAPK (Thr180/Tyr182) and GR (S-211) was further evaluated. Apoptosis was confirmed by immunolocalization of active CASPASE-3 and the subsequent cleavage of poly (ADP-ribose) polymerase (PARP) following intravitreal injection of triamcinolone acetonide (IVTA), in an early diabetic rat model (26 days after induction of diabetes).

Results: : IVTA significantly down-regulated mRNA expression of Caspase 3. Activation of CASPASE-3, the subsequent cleavage of PARP-1 and phosphorylation of p38MAPK, induced by diabetes, were attenuated by IVTA treatment, concomitant with the activation by phosphorylation of the glucocorticoid receptor (GR S-211).

Conclusions: IVTA exerts neural protective effects on retinal neurons. Inhibition of the p38MAPK pathway and activation of GR play a critical anti¬apoptotic role in retinal neurons of diabetes following IVTA treatment. Both the anti-inflammatory and anti-apoptotic effects of glucocorticoids may be mediated through inhibition of the p38MAPK pathway in diabetic retinopathy.

Keywords: 499 diabetic retinopathy • 426 apoptosis/cell death  

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