Sac-0601 prevents retinal vascular leakage in a mouse model of diabetic retinopathy

Sony Maharjan, Sujin Lee, Vijayendra Agrawal, Hyun Jung Choi, Yong Sun Maeng, Kyeojin Kim, Nam Jung Kim, Young Ger Suh, Young Guen Kwon

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Endothelium integrity is important for the normal functioning of vessels, the disruption of which can lead to disease. The blood-retinal barrier required for normal retinal function is compromised in diabetic retinopathy, causing retinal vascular leakage. Previously, we demonstrated the ability of Sac-0601[((2R,3S)-3-acetoxy-6-((3S,10R,13R,17R)-10,13-dimethyl-17-((R) -6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H- cyclopenta[a]phenanthren-3-yloxy)-3,6-dihydro-2H-pyran-2-yl)methyl acetate], a pseudo-sugar derivative of cholesterol, to increase survival of retinal endothelial cells. In the present study, we evaluated the ability of Sac-0601 to prevent retinal vascular leakages in vitro and in vivo. Sac-0601 treatment blocked VEGF-induced formation of actin stress fibers and stabilized the cortical actin ring in retinal endothelial cells. It also inhibited degradation of occludin, an important tight junction protein, and blocked VEGF-induced disruption of its linear pattern at the cell border. The [14C] sucrose permeability assay demonstrated that Sac-0601 was able to prevent VEGF-induced retinal endothelial permeability. The compound inhibited the vascular leakage in retina of mice intravitreally injected with VEGF. And it also significantly reduced the leakage in retina of diabetic retinopathy mice model. Taken together, our findings suggest the potential therapeutic usefulness of Sac-0601 for retinal vascular permeability diseases.

Original languageEnglish
Pages (from-to)35-40
Number of pages6
JournalEuropean Journal of Pharmacology
Volume657
Issue number1-3
DOIs
Publication statusPublished - 2011 Apr 25

Fingerprint

Retinal Vessels
Diabetic Retinopathy
Vascular Endothelial Growth Factor A
Retina
Actins
Permeability
Endothelial Cells
Blood-Retinal Barrier
Occludin
Tight Junction Proteins
Stress Fibers
Capillary Permeability
Vascular Diseases
Endothelium
Blood Vessels
Sucrose
Sac-0601
Cholesterol

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Maharjan, Sony ; Lee, Sujin ; Agrawal, Vijayendra ; Choi, Hyun Jung ; Maeng, Yong Sun ; Kim, Kyeojin ; Kim, Nam Jung ; Suh, Young Ger ; Kwon, Young Guen. / Sac-0601 prevents retinal vascular leakage in a mouse model of diabetic retinopathy. In: European Journal of Pharmacology. 2011 ; Vol. 657, No. 1-3. pp. 35-40.
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Maharjan, S, Lee, S, Agrawal, V, Choi, HJ, Maeng, YS, Kim, K, Kim, NJ, Suh, YG & Kwon, YG 2011, 'Sac-0601 prevents retinal vascular leakage in a mouse model of diabetic retinopathy', European Journal of Pharmacology, vol. 657, no. 1-3, pp. 35-40. https://doi.org/10.1016/j.ejphar.2011.01.040

Sac-0601 prevents retinal vascular leakage in a mouse model of diabetic retinopathy. / Maharjan, Sony; Lee, Sujin; Agrawal, Vijayendra; Choi, Hyun Jung; Maeng, Yong Sun; Kim, Kyeojin; Kim, Nam Jung; Suh, Young Ger; Kwon, Young Guen.

In: European Journal of Pharmacology, Vol. 657, No. 1-3, 25.04.2011, p. 35-40.

Research output: Contribution to journalArticle

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