Protective effect of clusterin on blood-retinal barrier breakdown in diabetic retinopathy

Jeong Hun Kim, Jin Hyoung Kim, Young Suk Yu, Bon Hong Min, Kyu Won Kim

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Purpose. To investigate whether clusterin attenuates blood-retinal barrier (BRB) breakdown in diabetic retinopathy. Methods. Mice with streptozotocin-induced diabetes and advanced glycation end product-treated human retinal microvascular endothelial cells (HRMECs) were used to determine the effect of clusterin on vascular permeability and tight junction protein expression, through perfusion of retinal vessels with FITC-bovine serum albumin, a [3H]sucrose permeability assay, a cell viability assay, Western blot analysis, immunocytochemistry, immunohistochemistry, and terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling. Results. Up to 20 μg/mL of clusterin, which is 20 times the effective therapeutic concentration, did not affect the viability of the HRMECs. Moreover, it caused no toxicity in the retina. It effectively inhibited vascular endothelial growth factor-induced hyperpermeability in the HRMECs and the retinas. The antipermeability activity of clusterin was related to the restoration of tight junction proteins. Finally, it was shown to reduce leakage from the vessels in the diabetic retinas and to restore the expression of the tight junction proteins. Conclusions. The data suggest that clusterin, a well-known antipermeability factor naturally secreted by cells, may have therapeutic potential in the treatment of diabetic BRB breakdown.

Original languageEnglish
Pages (from-to)1659-1665
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume51
Issue number3
DOIs
Publication statusPublished - 2010 Mar 1

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ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Medicine(all)

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