Pigment epithelium-derived factor protects retinal pigment epithelium from oxidant-mediated barrier dysfunction.
Retinal pigment epithelium (RPE) cells form a monolayer at the blood-retina barrier between the retina and choriocapillaries. The barrier function may be damaged by multiple stresses to the cell, including the repeated exposure to oxidants that are generated by photoreceptor cell turnover. The purpose of our study was to document the protective effect of pigment epithelium-derived factor (PEDF), a tropic factor produced by the RPE, on H(2)O(2)-induced RPE barrier dysfunction. When assayed by a FITC-labeled dextran transepithelial flux, the increased permeability of the RPE barrier (induced by H(2)O(2)) was prevented by PEDF pretreatment. To further explore the mechanism leading to this permeability change, we investigated the distribution of cytoskeleton and junctional proteins. The redistribution of the two junctional proteins occludin, and N-cadherin and actin reorganization in RPE, induced by H(2)O(2), can be prevented by PEDF pretreatment. PEDF can also prevent H(2)O(2)-induced stress kinase p38/27-kDa heat shock protein signaling which is known to mediate actin rearrangement. These findings indicated that PEDF can stabilize actin, maintain normal membrane occludin and N-cadherin structure, and preserve the barrier function of RPE cells against oxidative stress.
Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan.
Tsung-Chuan
TC
Ho
Yuh-Cheng
YC
Yang
Huey-Chuan
HC
Cheng
Ai-Ching
AC
Wu
Show-Li
SL
Chen
Yeou-Ping
YP
Tsao
D000199:Actins / Q000378:metabolism; D001813:Blood-Retinal Barrier / Q000187:drug effects / Q000502:physiology*; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D005136:Eye Proteins / Q000502:physiology*; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007365:Intercellular Junctions / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018832:Molecular Chaperones; D009363:Neoplasm Proteins / Q000378:metabolism; D009414:Nerve Growth Factors / Q000502:physiology*; D062793:Occludin; D016877:Oxidants / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D011725:Pyridines / Q000494:pharmacology; D015843:Serpins / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
D000199:Actins; D015820:Cadherins; D005136:Eye Proteins; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006861:Hydrogen Peroxide; D007093:Imidazoles; D007211:Indoles; D008565:Membrane Proteins; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D009414:Nerve Growth Factors; D062793:Occludin; D016877:Oxidants; D011725:Pyridines; D015843:Serpins; D048051:p38 Mitogen-Activated Protein Kinases; D000099174:Pigment Epithelium-Derived Factor; C057725:HSPB1 protein, human; C568985:OCLN protein, human; C007293:DAPI; C093642:SB 203580