March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Novel Curcumin Analogs for Treatment of Diabetic Retinopathy
Author Affiliations & Notes
  • Danyang Chen
    Charlesson, LLC, Oklahoma City, Oklahoma
  • Erica Little
    Charlesson, LLC, Oklahoma City, Oklahoma
  • Yan Zhang
    Charlesson, LLC, Oklahoma City, Oklahoma
  • Footnotes
    Commercial Relationships  Danyang Chen, Charlesson, LLC (E); Erica Little, Charlesson, LLC (E); Yan Zhang, Charlesson, LLC (E)
  • Footnotes
    Support  NIH 1R43EY019417-01
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 3295. doi:
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      Danyang Chen, Erica Little, Yan Zhang; Novel Curcumin Analogs for Treatment of Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3295.

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

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Abstract

Purpose: : Diabetic retinopathy (DR) is a common complication of diabetes mellitus and the most common cause of visual impairment. Although the exact mechanism involved in the development of DR is not known, several biochemical pathways, such as oxidative stress, over-expression of vascular endothelial growth factor (VEGF) and inflammation, are implicated. Curcumin has a wide range of pharmacologic effects. However, due to its poor bioavailability and unstability, the clinical application of curcumin is limited. To develop novel antioxidant and anti-angiogenic agents for the treatment of diabetic retinopathy, a series of curcumin analogs were designed and screened.

Methods: : MTT assay was used to determine the cell viability. The intracellular generation of reactive oxygen species (ROS) stimulated by tumor necrosis factor-alpha (TNF-α) was used to determine the antioxidant activity. The expression of VEGF was detected by ELISA.

Results: : Among a series of compounds screened, three analogs CLT010-01, CLT010-07 and CLT010-12 showed a more potent inhibition of the proliferation of cycling retinal capillary endothelial cells than curcumin and aminoguanidine (an inhibitor of inducible nitric oxide synthase). These analogs did not significantly inhibit the growth of pericytes, suggesting potential selectivity of endothelial growth inhibition. CLT010-01, CLT010-07 and CLT010-12 inhibited TNF-α-stimulated ROS production and down-regulated the expression of VEGF in cultured cells.

Conclusions: : Several novel curcumin analogs have anti-oxidant and anti-angiogenic activities. The in vivo efficacy of these compounds deserves to be evaluated in diabetic animal models.

Keywords: diabetic retinopathy • antioxidants • drug toxicity/drug effects 
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