Pigment Epithelium-Derived Factor Supports Normal Development of Photoreceptor Neurons and Opsin Expression after Retinal Pigment Epithelium Removal

Jablonski, Monica M.; Tombran-Tink, Joyce; Mrazek, David A.; Iannaccone, Alessandro

doi:10.1523/jneurosci.20-19-07149.2000

Cited by 140 publications

(86 citation statements)

References 51 publications

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“…It is anticipated that LBD peptides will prove to be useful for probing the involvement of PEDF-R in other PEDF-mediated cellular effects. For example, P1 blocked PEDF-mediated axon growth on primary retinal ganglion cells, 4 supporting the idea that PEDF specifically interacts with PEDF-R to induce neurotrophic effects.…”

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confidence: 55%

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Pigment Epithelium-derived Factor (PEDF) Prevents Retinal Cell Death via PEDF Receptor (PEDF-R)

Subramanian

Locatelli-Hoops

Kenealey

et al. 2013

Journal of Biological Chemistry

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Background: PEDF has neurotrophic activity and interacts with PEDF-R, a membrane-linked lipase. Results: A PEDF-binding region of PEDF-R is required for PEDF-R enzymatic stimulation, and peptides derived from this region block PEDF⅐PEDF-R-mediated retinal survival activities. Conclusion: A ligand binding domain is identified in PEDF-R, a critical receptor for the survival activity of PEDF. Significance: The findings provide mechanistic insight into the survival activity of PEDF.

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confidence: 55%

“…In both systems, the Bcl-2 signal induced nuclear translocation of apoptosis-inducing factor, a caspase-independent apoptosis inducer (40). Although these studies did not report a receptor for PEDF signaling, our findings demonstrate that PEDF-R can mediate these effects, 4 Y. Yin, personal communication. FIGURE 8.…”

mentioning

confidence: 60%

Pigment Epithelium-derived Factor (PEDF) Prevents Retinal Cell Death via PEDF Receptor (PEDF-R)

Subramanian

Locatelli-Hoops

Kenealey

et al. 2013

Journal of Biological Chemistry

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“…Collectively, Trx released from the RPE cells contributes to the cytoprotection of photoreceptor cells by eliminating oxidative stress. The RPE releases several neurotrophic factors such as nerve growth factor (NGF), brain-derived growth factor, neurotrophin-3 (Ishida et al, 1997), and pigment epitheliumderived factor (Jablonski et al, 2000). These neurotrophic factors confer cytoprotection against light-induced photoreceptor cell damage (LaVail et al, 1992;Cao et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Cytoprotective Effects of Geranylgeranylacetone against Retinal Photooxidative Damage

Tanito¹,

Kwon²,

Kondo³

et al. 2005

J. Neurosci.

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Exposure to excessive light induces retinal photoreceptor cell damage, leading to development and progression of various retinal diseases. We tested the effect of geranylgeranylacetone (GGA), an acyclic polyisoprenoid, on light-induced retinal damage in mice. Oral treatment with GGA (1.0 mg/d) for 5 d induced thioredoxin (Trx) and heat shock protein 72 (Hsp72) predominantly in the retinal pigment epithelium (RPE). After white light exposure (8000 lux for 2 h), the percentage of terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive photoreceptor cells decreased significantly at 24 and 96 h, and the number of photoreceptor cell nuclei at 96 h and the electroretinographic amplitudes of the a- and b-waves at 4 and 10 d increased significantly in GGA-pretreated mice compared with saline-pretreated mice. Light-induced upregulations of 8-hydroxy-2-deoxyguanosine and 4-hydroxy-2-nonenal-modified protein, markers of oxidative stress, were inhibited by GGA pretreatment. To elucidate the cytoprotective mechanism of GGA and Trx, we used human K-1034 RPE cells and mouse photoreceptor-derived 661W cells. In K-1034 cells, GGA (10 μm) induced intracellular Trx, Hsp72, and extracellular Trx but not extracellular Hsp72. Extracellular Trx (0.75 nm) attenuated H2O2(200 μm)-induced cell damage in 661W cells. Pretreatment with GGA and overexpression of Trx in K-1034 cells counteracted H2O2(50 μm)-induced attenuation of cellular latex bead incorporation. Protection of phagocytotic activity through induction of Trx and possibly Hsp72 in RPE cells and elimination of oxidative stress in the photoreceptor layer through release of Trx from RPE cells may be mechanisms of GGA-mediated cytoprotection. Therefore, Trx is a neurotrophic factor released from RPE cells and plays a crucial role in maintaining photoreceptor cell integrity.

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“…Interestingly, in several cases the pigmented part of the implant had detached itself from the transdifferentiated part so that the implant resembled a small ''inverted eye'' with the ONL facing the inner cavity of the implant. Since it has been demonstrated that the RPE secretes the pigment epithelium-derived factor (PEDF) that exerts a very powerful morphogenetic effect on photoreceptors of the embryonic eye (Jablonski et al, 2000;Karakousis et al, 2001), the differentiation of the ONL in our polarized implants could have been promoted by the PEDF produced by the pigmented part of the implant and accumulated in the implant's inner cavity. Moreover, the differentiation of the new-forming laminar retina could also have been promoted by locally acting factors.…”

Section: Discussionmentioning

confidence: 99%

Pigmented epithelium to retinal transdifferentiation and Pax6 expression in larval Xenopus laevis

Arresta

Bernardini

et al. 2005

J. Exp. Zool.

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This study examines the retinal transdifferentiation (TD) of retinal pigmented epithelium (RPE) fragments dissected from Xenopus laevis larvae and implanted into the vitreous chamber of non-lentectomized host eyes. In these experimental conditions, most RPE implants transformed into polarized vesicles in which the side adjacent to the lens maintained the RPE phenotype, while the side adjacent to the host retina transformed into a laminar retina with the photoreceptor layer facing the cavity of the vesicle and with the ganglionar cell layer facing the host retina. The formation of a new retina with a laminar organization is the result of depigmentation, proliferation and differentiation of progenitor cells under the influence of inductive factors from the host retina. The phases of the TD process were followed using BrdU labelling as a marker of the proliferation phase and using a monoclonal antibody (mAbHP1) as a definitive indicator of retina formation. Pigmented RPE cells do not express Pax6. In the early phase of RPE to retinal TD, all depigmented and proliferating progenitor cells expressed Pax6. Changes in the Pax6 expression pattern became apparent in the early phase of differentiation, when Pax6 expression decreased in the presumptive outer nuclear layer (ONL) of the new-forming retina. Finally, during the late differentiation phase, the ONL, which contains photoreceptors, no longer expressed Pax6, Pax6 expression being confined to the ganglion cell layer and the inner nuclear layer. It is well known that larval and adult newts are able to regenerate the neural retina (NR) from the retinal pigmented epithelium (RPE) through a transdifferentiation (TD) process (Stone, '50; Hasegawa, '58; Reyer, '77; Stroeva and Mitashov, '83) and that the RPE of larval and adult frogs transdifferentiates into NR when implanted into the vitreous chamber of a host tadpole (Lopashov and Sologub, '72; Sologub, '77). The regeneration of NR via TD from RPE also occurs in the chick and rat embryos, but this capacity is restricted to early stages of ocular development prior to the irreversible commitment of the RPE to the pigmented cell fate (Park and Hollenberg, '89; Pittack et al., '91; Zhao et al., '95). Some recent studies have begun to investigate the molecular nature of factors involved in this TD process. The basic fibroblast growth factor (FGF2) has been demonstrated to be a potent factor capable of triggering the retinal TD of the embryonic chick RPE both in vivo and in vitro (Park and Hollenberg, '89; Pittack et al., '91; Araki et al., '98), as well as triggering the retinal TD of the embryonic rat RPE cultured in vitro (Zhao et al., '95). Sakaguchi et al. ('97) demonstrated that FGF2 also promoted retinal TD of larval Xenopus laevis RPE cultured in vitro, supporting the idea that retinal TD undergone by X. laevis RPE fragments implanted into the vitreous chamber of host tadpoles is the result of retinal-derived FGF2 accumulated into the vitreous chamber. However, the retina regeneration in newts is a u...

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Pigment Epithelium-Derived Factor Supports Normal Development of Photoreceptor Neurons and Opsin Expression after Retinal Pigment Epithelium Removal

Cited by 140 publications

References 51 publications

Pigment Epithelium-derived Factor (PEDF) Prevents Retinal Cell Death via PEDF Receptor (PEDF-R)

Pigment Epithelium-derived Factor (PEDF) Prevents Retinal Cell Death via PEDF Receptor (PEDF-R)

Cytoprotective Effects of Geranylgeranylacetone against Retinal Photooxidative Damage

Pigmented epithelium to retinal transdifferentiation and Pax6 expression in larval Xenopus laevis

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