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

Fingerprint

Blood-Retinal Barrier
Clusterin
Diabetic Retinopathy
Tight Junction Proteins
Retina
Endothelial Cells
Immunohistochemistry
Retinal Vessels
Advanced Glycosylation End Products
Experimental Diabetes Mellitus
DNA Nucleotidylexotransferase
Fluorescein-5-isothiocyanate
Capillary Permeability
Biotin
Bovine Serum Albumin
Vascular Endothelial Growth Factor A
Sucrose
Permeability
Cell Survival
Therapeutics

ASJC Scopus subject areas

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

Cite this

Protective effect of clusterin on blood-retinal barrier breakdown in diabetic retinopathy. / Kim, Jeong Hun; Kim, Jin Hyoung; Yu, Young Suk; Min, Bon Hong; Kim, Kyu Won.

In: Investigative Ophthalmology and Visual Science, Vol. 51, No. 3, 01.03.2010, p. 1659-1665.

Research output: Contribution to journalArticle

Kim, Jeong Hun ; Kim, Jin Hyoung ; Yu, Young Suk ; Min, Bon Hong ; Kim, Kyu Won. / Protective effect of clusterin on blood-retinal barrier breakdown in diabetic retinopathy. In: Investigative Ophthalmology and Visual Science. 2010 ; Vol. 51, No. 3. pp. 1659-1665.
@article{e3efa00ff08c402788e90a13142214df,
title = "Protective effect of clusterin on blood-retinal barrier breakdown in diabetic retinopathy",
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.",
author = "Kim, {Jeong Hun} and Kim, {Jin Hyoung} and Yu, {Young Suk} and Min, {Bon Hong} and Kim, {Kyu Won}",
year = "2010",
month = "3",
day = "1",
doi = "10.1167/iovs.09-3615",
language = "English",
volume = "51",
pages = "1659--1665",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "3",

}

TY - JOUR

T1 - Protective effect of clusterin on blood-retinal barrier breakdown in diabetic retinopathy

AU - Kim, Jeong Hun

AU - Kim, Jin Hyoung

AU - Yu, Young Suk

AU - Min, Bon Hong

AU - Kim, Kyu Won

PY - 2010/3/1

Y1 - 2010/3/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77949893843&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949893843&partnerID=8YFLogxK

U2 - 10.1167/iovs.09-3615

DO - 10.1167/iovs.09-3615

M3 - Article

C2 - 19875648

AN - SCOPUS:77949893843

VL - 51

SP - 1659

EP - 1665

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 3

ER -