Curcumin Inhibits Neuronal Loss in the Retina and Elevates Ca²⁺/Calmodulin-Dependent Protein Kinase II Activity in Diabetic Rats

J Ocul Pharmacol Ther. 2015 Nov;31(9):555-62. doi: 10.1089/jop.2015.0006. Epub 2015 Jul 24.

Abstract

Purpose: To determine whether curcumin offers neuroprotection to minimize the apoptosis of neural cells in the retina of diabetic rats.

Methods: Streptozotocin (STZ)-induced diabetic rats and control rats were used in this study. A subgroup of STZ-induced diabetic rats were treated with curcumin for 12 weeks. Retinal histology, apoptosis of neural cells in the retina, electroretinograms, and retinal glutamate content were evaluated after 12 weeks. Retinal levels of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), phospho-CaMKII (p-CaMKII), and cleaved caspase-3 were determined by Western blot analysis.

Results: The amplitudes a-wave, b-wave, and oscillatory potential were reduced by diabetes, but curcumin treatment suppressed this reduction of amplitudes. Curcumin also prevented cell loss from the outer nuclear, inner nuclear, and ganglion cell layers. Apoptosis of retinal neurons was detected in diabetic rats. The concentration of glutamate in the retina was higher in diabetic rats, but was significantly reduced in the curcumin-treated group. Furthermore, p-CaMKII and cleaved caspase-3 expression were upregulated in the diabetic retina, but reduced in curcumin-treated rats.

Conclusions: Curcumin attenuated diabetes-induced apoptosis in retinal neurons by reducing the glutamate level and downregulating CaMKII. Thus, curcumin might be used to prevent neuronal damage in the retina of patients with diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Caspase 3 / genetics
  • Curcumin / pharmacology*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Down-Regulation / drug effects
  • Gene Expression Regulation / drug effects
  • Male
  • Neurons / drug effects
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Retina / drug effects*
  • Retina / pathology
  • Streptozocin
  • Up-Regulation / drug effects

Substances

  • Neuroprotective Agents
  • Streptozocin
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Caspase 3
  • Curcumin