Decrease of pigment epithelium-derived factor in aqueous humor with increasing age

Ogata, Nahoko; Matsuoka, Masato; Imaizumi, Masahito; Arichi, Miwa; Matsumura, Miyo

doi:10.1016/j.ajo.2003.08.058

Cited by 26 publications

(19 citation statements)

References 4 publications

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“…4 Previous studies showed that PEDF levels are decreased in the vitreous of diabetic retinopathy patients, 42 in the aging aqueous humor and choroid, 13 and in the eyes of patients with AMD. 43 Furthermore, db/db mice and OIR rats showed decreased levels of PEDF in the retina.…”

Section: Discussionmentioning

confidence: 99%

“…This observation supports our previous notion that decreased PEDF levels contribute to retinal neovascularization in the OIR model. [11][12][13]15,16 In the laser-induced CNV model, it was shown that CNV represents a wound healing response. 48,49 Previous studies have reported a significant decrease in PEDF immunoreactivity in the choroid from AMD human donors and rats with laser-induced CNV.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 It has been suggested that an age-related decline of PEDF in the aqueous humor may account for less PEDF-mediated neurotrophic and antiangiogenic activities, predisposing the aging eye to ocular diseases. 13 In db/db mice, a mouse model of type 2 diabetes mellitus, 14 lower vitreous levels of PEDF are associated with early-onset diabetic retinopathy. 15 In the oxygen-induced retinopathy (OIR) model, decreased protein levels of PEDF in the retina are associated with ischemia-induced retinal neovascularization.…”

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confidence: 99%

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Overexpression of Pigment Epithelium–Derived Factor Inhibits Retinal Inflammation and Neovascularization

Park

Jin

et al. 2011

The American Journal of Pathology

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Pigment epithelium-derived factor (PEDF) is a serine proteinase inhibitor with antiangiogenic activities. To investigate whether PEDF overexpression has an impact on ocular neovascularization in vivo, we generated PEDF transgenic (PEDF-Tg) mice that ubiquitously express human PEDF driven by the ␤-actin promoter. The PEDF-Tg mice under normal conditions did not show any abnormalities in retinal histologic findings or visual function. In contrast, PEDF-Tg animals with oxygen-induced retinopathy (OIR) developed significantly less severe retinal neovascularization compared with wild-type (Wt) mice with OIR. In addition, PEDF-Tg mice with OIR had significantly lower vascular leakage in the retina but higher occludin levels than the Wt mice with OIR, suggesting a protective effect on the bloodretinal barrier. Furthermore, retinal levels of proinflammatory factors were significantly lower in PEDF-Tg mice with OIR than in the Wt mice with OIR. In the laser-induced choroidal neovascularization (CNV) model, the CNV area was significantly smaller in the PEDF-Tg mice than in the Wt mice. Also, the laser burn-induced overexpression of proangiogenic and inflammatory factors was observed in the retina and retinal pigment epithelium of Wt mice but not in PEDF-Tg mice. Taken together, these results suggest that overexpression of PEDF inhibits retinal inflammation and neovascularization in both the OIR and laser-induced CNV models. The PEDF-Tg mice provide a useful model for studying the roles of angiogenic inhibitors in neovascular disorders such as diabetic retinopathy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Overexpression of Pigment Epithelium–Derived Factor Inhibits Retinal Inflammation and Neovascularization

Park

Jin

et al. 2011

The American Journal of Pathology

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“…It has also been reported that PEDF has broad beneficial effects including anticancer, antioxidation, anti-inflammation, and antifibrosis activities (23,44,70,80). Furthermore, PEDF levels are decreased in the aqueous and vitreous fluids from patients with DR and in the retinae of DR animal models (22,52,53). Therefore, decreased PEDF levels have been suggested to contribute to DR (9,10,27,64).…”

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confidence: 99%

Identification of a Novel Inhibitor of the Canonical Wnt Pathway

Park

Lee

Zhang

et al. 2011

Molecular and Cellular Biology

117

129

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Wnt signaling is known to regulate multiple processes including angiogenesis, inflammation, and fibrosis. Here, we identified a novel inhibitor of the Wnt pathway, pigment epithelium-derived factor (PEDF), a multifunctional serine proteinase inhibitor. Both overexpression of PEDF in transgenic mice and administration of PEDF protein attenuated Wnt signaling induced by retinal ischemia. Furthermore, PEDF knockdown by small interfering RNA (siRNA) and PEDF knockout in PEDF ؊/؊ mice induced activation of Wnt signaling. PEDF bound to LRP6, a Wnt coreceptor, with high affinity (K d [dissociation constant] of 3.7 nM) and blocked the Wnt signaling induced by Wnt ligand. The physical interaction of PEDF with LRP6 was confirmed by a coprecipitation assay, which showed that PEDF bound to LRP6 at the E1E2 domain. In addition, binding of PEDF to LRP6 blocked Wnt ligand-induced LRP6-Frizzled receptor dimerization, an essential step in Wnt signaling. These results suggest that PEDF is an endogenous antagonist of LRP6, and blocking Wnt signaling may represent a novel mechanism for its protective effects against diabetic retinopathy.

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“…These interactions could have positive implications on the conformation and quality of its ECM, which could influence aqueous humor outflow and mediate DEXinduced elevated IOP. To this effect, it is interesting to note that the levels of PEDF have been reported to be significantly lower in the aqueous humor of individuals of increasing age 16 and in patients with advanced glaucoma. 17 Furthermore, MMP-9, which degrades PEDF, has been found significantly upregulated in the leucocytes of normal tension glaucoma patients, 18 and, more recently, MMP-9 has been genetically linked to patients with acute primary angle closure glaucoma.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone Increases Pigment Epithelium-Derived Factor in Perfused Human Eyes

Perruccio

Rowlette

Comes

et al. 2008

Current Eye Research

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Purpose-To investigate the effects of dexamethasone (DEX) on pigment epithelium-derived factor (PEDF) cDNA and secreted protein in human trabecular meshwork (TM).Methods-Anterior segment organ cultures were perfused with 0.1 μM DEX (OD) and vehicle (OS). Primary human TM cells (HTM) were treated with DEX under similar conditions. PEDF mRNA and secreted PEDF protein were quantitated by RT-PCR and Western blot.Results-PEDF mRNA and secreted PEDF protein levels were significantly higher in DEX over vehicle-treated cultures. In contrast, DEX decreased the activity of a 92-kDa gelatinolytic zymogen in organ culture effluents.Conclusion-DEX action in the human TM might include a PEDF-mediating pathway.

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Decrease of pigment epithelium-derived factor in aqueous humor with increasing age

Cited by 26 publications

References 4 publications

Overexpression of Pigment Epithelium–Derived Factor Inhibits Retinal Inflammation and Neovascularization

Overexpression of Pigment Epithelium–Derived Factor Inhibits Retinal Inflammation and Neovascularization

Identification of a Novel Inhibitor of the Canonical Wnt Pathway

Dexamethasone Increases Pigment Epithelium-Derived Factor in Perfused Human Eyes

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