Amyloid-β-induced matrix metalloproteinase-9 secretion is associated with retinal pigment epithelial barrier disruption

  • Authors:
    • Lining Cao
    • Hao Wang
    • Fang Wang
  • View Affiliations

  • Published online on: March 20, 2013     https://doi.org/10.3892/ijmm.2013.1310
  • Pages: 1105-1112
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Local and chronic inflammation induced by amyloid-β (Aβ) plays a central role in the development of age-related macular degeneration. The retina is an immune-privileged site due to local tissue barrier. Yet, the manner by which immune cells pass through this barrier and accumulate in the retina remains unclear. Matrix metalloproteinases (MMPs) induce barrier disruption via proteolysis of epithelial tight junction (TJ) proteins. We hypothesized that Aβ-induced MMP secretion causes disruption of epithelial barrier integrity. To test this hypothesis, human adult retinal pigment epithelial (haRPE) cells were exposed to Aβ, and the expression of MMP-2 and MMP-9 was detected using gelatin zymography. To demonstrate the key role of MMPs in modulating epithelial barrier structure, the MMP agonist 4-aminophenylmercuric acetate (APMA), an MMP inhibitor (GM6001) and siRNA against MMP-9 were employed for comparison. We found that MMP-9, secreted by Aβ- or APMA-stimulated cells, mediated low transepithelial electrical resistance (TER) and high transepithelial permeability by disrupting TJ proteins. However, these alterations were reduced by the MMP inhibitor GM6001 or by silencing of the MMP-9 gene. Our findings suggest that the degradation of TJ proteins such as zonula occludens-1, occludin and F-actin by MMP-9 secreted by Aβ-stimulated cells constitutes an important mechanism in the breakdown of the barrier which contributes to chronic inflammation in the retina of age-related macular degeneration.
View Figures
View References

Related Articles

Journal Cover

May 2013
Volume 31 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Cao L, Wang H and Wang F: Amyloid-β-induced matrix metalloproteinase-9 secretion is associated with retinal pigment epithelial barrier disruption. Int J Mol Med 31: 1105-1112, 2013
APA
Cao, L., Wang, H., & Wang, F. (2013). Amyloid-β-induced matrix metalloproteinase-9 secretion is associated with retinal pigment epithelial barrier disruption. International Journal of Molecular Medicine, 31, 1105-1112. https://doi.org/10.3892/ijmm.2013.1310
MLA
Cao, L., Wang, H., Wang, F."Amyloid-β-induced matrix metalloproteinase-9 secretion is associated with retinal pigment epithelial barrier disruption". International Journal of Molecular Medicine 31.5 (2013): 1105-1112.
Chicago
Cao, L., Wang, H., Wang, F."Amyloid-β-induced matrix metalloproteinase-9 secretion is associated with retinal pigment epithelial barrier disruption". International Journal of Molecular Medicine 31, no. 5 (2013): 1105-1112. https://doi.org/10.3892/ijmm.2013.1310