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 language | English |
|---|---|
| Pages (from-to) | 1659-1665 |
| Number of pages | 7 |
| Journal | Investigative Ophthalmology and Visual Science |
| Volume | 51 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2010 Mar 1 |
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ASJC Scopus subject areas
- Ophthalmology
- Sensory Systems
- Cellular and Molecular Neuroscience
- Medicine(all)
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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 journal › Article
}
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.
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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 -