Pigment epithelium-derived factor inhibits oxidative stress-induced cell death by activation of extracellular signal-regulated kinases in cultured retinal pigment epithelial cells

Tsao, Yeou‐Ping; Ho, Tzyy‐Chang; Chen, Show‐Li; Cheng, Huey-Chuan

doi:10.1016/j.lfs.2006.01.041

Cited by 87 publications

(70 citation statements)

References 26 publications

(41 reference statements)

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“…45,62,63 PEDF can protect RGC from death after glutamate toxicity, ischemia, trophic factor withdrawal, and in mouse models of glaucoma and inherited retinal degeneration. 35,38,[64][65][66][67] In vitro and in vivo, optimal RGC neuroprotective dosages of PEDF were 2.5 3 10 À5 lg/lL and 1 lg/lL, respectively. Others report that in vivo, 0.001 lg/lL is required to protect RGC from excitotoxicity and serum withdrawal, 36 a concentration of PEDF that is also neuroprotective for photoreceptors, cerebellar granule cells, and hippocampal neurons.…”

Section: Discussionmentioning

confidence: 99%

Pigment Epithelium-Derived Factor Is Retinal Ganglion Cell Neuroprotective and Axogenic After Optic Nerve Crush Injury

Vigneswara¹,

Berry²,

Logan³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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Citation: Vigneswara V, Berry M, Logan A, Ahmed Z. Pigment epithelium-derived factor is retinal ganglion cell neuroprotective and axogenic after optic nerve crush injury. Invest Ophthalmol Vis Sci. 2013;54: 262454: -263354: . DOI: 10.1167 PURPOSE. To investigate neuroprotective and axogenic properties of pigment epitheliumderived factor (PEDF) in retinal ganglion cells (RGC) in vitro and in vivo.METHODS. Adult rat retinal cultures were treated with combinations of PBS and PEDF with or without a cell permeable analogue of cAMP, and RGC survival and neurite lengths quantified. The optic nerves of anesthetised rats were also crushed intraorbitally to transect all RGC axons followed by intravitreal injections of either PBS, PEDF, or cAMPþPEDF every 7 days. RGC were back filled with FluoroGold to quantify RGC survival and longitudinal optic nerve sections were stained with GAP43 antibodies to detect regenerating RGC axons.RESULTS. An optimal dose of 2.5 3 10 À5 lg/lL, promoted 65% more RGC survival than controls in vitro, increasing by 4.4-and 5-fold the number of RGC with neurites and the mean neurite length, respectively. Addition of cAMP with or without PEDF did not potentiate RGC survival or the mean number of RGC with neurites, but enhanced RGC neurite length by 1.4-fold, compared with PEDF alone. After optic nerve crush (ONC), PEDF protected RGC from apoptosis and increased the numbers of regenerating RGC axons in the optic nerve by 4.6-and 3.4-fold, respectively when compared with controls. cAMP did not enhance PEDF-induced RGC neuroprotection, but potentiated its neuroregenerative effects by 2-to 3-fold, increasing the number of RGC axons regenerating at 500 and 1000 lm from the lesions site.CONCLUSIONS. This study is the first to demonstrate that PEDF enhances both RGC survival and axon regeneration in vitro and in vivo.Keywords: PEDF, retinal ganglion cells, neuroprotection, axon regeneration, optic nerve R etinal ganglion cells (RGC) rapidly die after axotomy, but are protected by combinatorial treatments with neurotrophic factors (NTF), including brain-derived NTF (BDNF), neurotrophin-3/4 (NT-3/4), ciliary neurotrophic factor (CNTF), glial cell line-derived neurotrophic (GDNF), and basic fibroblast growth factor (FGF2). 1-7 NTF combinations also activate intrinsic axon growth signalling pathways that initiate RGC axon regeneration.1-7 Pigment epithelium-derived factor (PEDF) is a 50 kDa NTF glycoprotein belonging to the serpin superfamily, that protects a wide range of central nervous system (CNS) neurons. [8][9][10][11][12][13][14][15] Although first isolated from fetal human retinal pigment (choroid) epithelial cells, like many other NTF, PEDF is expressed in a wide variety of tissues including brain, spinal cord, skeletal muscle, heart, endothelial cells, and osteoblasts. [16][17][18][19][20] PEDF has an array of unique properties including neuroprotective, anti-angiogenic, antiinflammatory, anti-oxidative, and antitumorigenic activities. [21][22][23][24][25][26][27] PEDF is a multifaceted NTF that ...

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Section: Discussionmentioning

confidence: 99%

Pigment Epithelium-Derived Factor Is Retinal Ganglion Cell Neuroprotective and Axogenic After Optic Nerve Crush Injury

Vigneswara¹,

Berry²,

Logan³

et al. 2013

Invest. Ophthalmol. Vis. Sci.

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“…22 The PEDF cDNA was subcloned into the BamHI/NotI site of the AAV packaging plasmid (pAAV-Dϩ), allowing transcription of PEDF to be driven by the cytomegalovirus promoter. For generation of recombinant AAV, pAAV-D (ϩ)-hPEDF, and AAV helper plasmids (pXR5 and pXX6) were cotransfected into human embryonic kidney 293T cells.…”

Section: Generation Of Adeno-associated Virus Pedfmentioning

confidence: 99%

Pigment Epithelium-Derived Factor Is an Intrinsic Antifibrosis Factor Targeting Hepatic Stellate Cells

Chen

Shih

et al. 2010

The American Journal of Pathology

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The liver is the major site of pigment epithelium-derived factor (PEDF) synthesis. Recent evidence suggests a protective role of PEDF in liver cirrhosis. In the present study, immunohistochemical analyses revealed lower PEDF levels in liver tissues of patients with cirrhosis and in animals with chemically induced liver fibrosis. Delivery of the PEDF gene into liver cells produced local PEDF synthesis and ameliorated liver fibrosis in animals treated with either carbon tetrachloride or thioacetamide. In addition, suppression of peroxisome proliferator-activated receptor gamma expression, as well as nuclear translocation of nuclear factorkappa B was found in hepatic stellate cells (HSCs) from fibrotic livers, and both changes were reversed by PEDF gene delivery. In culture-activated HSCs, PEDF, through the induction of peroxisome proliferator-activated receptor gamma, reduced the activity of nuclear factorkappa B and prevented the nuclear localization of JunD. In conclusion, our observations that PEDF levels are reduced during liver cirrhosis and that PEDF gene delivery ameliorates cirrhosis suggest that PEDF is an intrinsic protector against liver cirrhosis. Direct inactivation of HSCs and the induction of apoptosis of activated HSCs may be two of the mechanisms by which PEDF suppresses liver cirrhosis. (Am J Pathol

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“…Given the central role RPE plays in AMD pathogenesis, a commonly used experimental model to study the link between oxidative stress and AMD involves the use of cultured human RPE (ARPE-19) cells. Common endpoints include cell survival, morphology, activation of signaling cascades, and cytokine production (Chan et al, 2008;Dong et al, 2011;Glotin et al, 2006;Jiang et al, 2009;Klettner and Roider, 2009;Qin et al, 2006;Tsao et al, 2006;Wang et al, 1998;Wu et al, 2010).…”

Section: Age-related Macular Degenerationmentioning

confidence: 99%

“…In response to oxidants such as hydrogen peroxide or tert-butyl hydroperoxide, MAPK (most notably ERKs and p38 MAPK) activation has been shown to either protect against or exacerbate oxidative injury, differentiated by the amount of RPE cell death (Chan et al, 2008;Dong et al, 2011;Glotin et al, 2006;Jiang et al, 2009;Klettner and Roider, 2009;Qin et al, 2006;Tsao et al, 2006;Wang et al, 1998;Wu et al, 2010). These findings also raise questions as to the impact of oxidative stress on the outer BRB when the MAPK pathway is modulated pharmacologically by a MEK inhibitor.…”

Section: Mapk Activation and Oxidative Stress Response In The Retinamentioning

confidence: 99%

Retinal Vein Occlusion Induced by a MEK Inhibitor - Impact of Oxidative Stress on the Blood-Retinal Barrier

Yang¹,

Huang²

2012

Oxidative Stress and Diseases

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Pigment epithelium-derived factor inhibits oxidative stress-induced cell death by activation of extracellular signal-regulated kinases in cultured retinal pigment epithelial cells

Cited by 87 publications

References 26 publications

Pigment Epithelium-Derived Factor Is Retinal Ganglion Cell Neuroprotective and Axogenic After Optic Nerve Crush Injury

Pigment Epithelium-Derived Factor Is Retinal Ganglion Cell Neuroprotective and Axogenic After Optic Nerve Crush Injury

Pigment Epithelium-Derived Factor Is an Intrinsic Antifibrosis Factor Targeting Hepatic Stellate Cells

Retinal Vein Occlusion Induced by a MEK Inhibitor - Impact of Oxidative Stress on the Blood-Retinal Barrier

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