RPE secreted proteins and antibody influence photoreceptor cell survival and maturation

Sheedlo, Harold J.; Nelson, Tammy Hancock; Lin, Nianwei; Rogers, Torrence A; Roque, Rouel S.; Turner, James

doi:10.1016/s0165-3806(97)00219-8

Cited by 35 publications

(26 citation statements)

References 42 publications

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“…The proliferation event could be controlled by specific growth factors as part of the cell suspension medium. For example, proteins secreted by neonatal rat RPE cells in vitro have been analyzed in retinal cell and explant paradigms, in vivo and by electrophoresis (Sheedlo et al 1992a(Sheedlo et al ,b, 1995(Sheedlo et al , 1998Turner 1995, 1996a,b). These proteins promoted neurite outgrowth and affected proliferation of progenitor cells from embryonic and neonatal rat retinal explants (Sheedlo and Turner 1996a,b).…”

Section: Discussionmentioning

confidence: 99%

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RPE-derived factors modulate photoreceptor differentiation: A possible role in the retinal stem cell niche

Sheedlo

Bartosh

Wang

et al. 2007

In Vitro Cell.Dev.Biol.-Animal

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A photoreceptor cell line, designated 661W, was tested for its response to growth factors secreted by retinal pigment epithelial cells including basic fibroblast growth factor, epidermal growth factor, and nerve growth factor. Early passaged 661W cells expressed high levels of retinal progenitor markers such as nestin and Pax6, but not opsin or glial fibrillary acidic protein. 661W cells grown in FGF-2 or EGF exhibited a multiple-process morphology with small phase-bright nuclei similar to neurons, whereas cells cultured in nerve growth factor (NGF) or retinal pigment epithelium (RPE)-conditioned medium (RPE-CM) displayed rounded profiles lacking processes. 661W cells grown in FGF-2 were slightly elevated, but not significantly above, control cultures; but cells treated with RPE-CM or NGF were fewer, approximately 63% and 49% of control, respectively. NGF immunodepletion of RPE-CM strongly suppressed the inhibitory activity of RPE-CM on cell proliferation. Cells treated with FGF-2, but not NGF, upregulated their expression of opsin. All treatment conditions resulted in almost 100% viability based on calcium AM staining. Cells grown on extracellular matrix proteins laminin, fibronectin, and/or collagen resembled those grown on untreated dishes. This study showed that early passaged 661W cells displayed characteristics of retinal progenitor cells. The 661W cells proliferated and appeared to mature morphologically expressing rod photoreceptor phenotype in response to FGF-2. In contrast, NGF and RPE-CM inhibited proliferation and morphological differentiation of 661W cells, possibly inducing cell cycle arrest. These findings are consistent with reports that the RPE modulates photoreceptor differentiation and retinal progenitor cells via secreted factors and may play a role in the regulation of the retinal stem cell niche.

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Section: Discussionmentioning

confidence: 99%

“…Cells were grown to confluence in DMEM containing 5-10% fetal bovine serum (FBS), rinsed thoroughly, and grown in DM for 2 d. The RPE-CM was collected, sterile filtered, and stored at −70°C. RPE-secreted proteins in the RPE-CM have been previously characterized (Sheedlo et al 1998).…”

Section: Methodsmentioning

confidence: 99%

RPE-derived factors modulate photoreceptor differentiation: A possible role in the retinal stem cell niche

Sheedlo

Bartosh

Wang

et al. 2007

In Vitro Cell.Dev.Biol.-Animal

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“…In all cases the rescue extends beyond the limits of the injection or transplant, suggesting that a diffusible factor is responsible for photoreceptor rescue. Moreover, it has been demonstrated that RPE-secreted proteins positively influence photoreceptor survival (Gaur et al, 1992;Sheedlo et al, 1992Sheedlo et al, , 1998. Although an abundance of data indicates that the RPE or "factors" supplied by the RPE are of paramount importance to the development and/or survival of photoreceptors, the nature of these interactions is poorly understood.…”

Section: Abstract: Photoreceptor; Pigment Epithelium-derived Factor;mentioning

confidence: 99%

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

et al. 2000

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Dysfunction of the retinal pigment epithelium (RPE), its loss, or separation from the underlying neural retina results in severe photoreceptor degeneration. Pigment epithelium-derived factor (PEDF) is a glycoprotein with reported neuroprotective and differentiation properties that is secreted in abundance by RPE cells. The "pooling" of PEDF within the interphotoreceptor matrix places this molecule in a prime physical location to affect the underlying neural retina. The purpose of this study was to analyze the morphogenetic activity of PEDF in a model of photoreceptor dysmorphogenesis induced by removal of the RPE. Eyes were dissected from embryonic Xenopus laevis, and the RPE was removed before culturing in medium containing PEDF, PEDF plus anti-PEDF antibodies, or medium alone. Control retinas were maintained with an adherent RPE. Light and electron microscopic analysis was used to examine retinal ultrastructure. Opsin was localized immunocytochemically and quantified as an index of outer segment membranous material and photoreceptor protein expression. Removal of the RPE resulted in an aberrant assembly of photoreceptor outer segments, loss of fine subcellular ultrastructure in photoreceptors, and a reduction in opsin protein levels when compared with control retinas. The addition of PEDF prevented the dysmorphic photoreceptor changes induced by RPE removal. In particular, photoreceptor ultrastructure, outer segment membrane assembly, and steady-state levels of opsin were equivalent to control conditions. Anti-PEDF antibodies completely blocked the morphogenetic activity of PEDF. These results indicate that PEDF is able to mimic the supportive role of the RPE on photoreceptors during the final stages of retinal morphogenesis.

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“…Dysfunction of the RPE causes severe retinal degeneration both in animals (D'Cruz et al, 2000;Roque and Caldwell, 1990), and humans (Gu et al, 1997;Kennedy et al, 1999;Marlhens et al, 1997). Moreover, it has been demonstrated that RPE-secreted proteins favorably affect photoreceptor survival (Cao et al, 1999;Gaur et al, 1992;Sheedlo et al, 1992;Sheedlo et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Pigment epithelium‐derived factor supports normal Müller cell development and glutamine synthetase expression after removal of the retinal pigment epithelium

Jablonski

Tombran-Tink

Mrazek

et al. 2001

Glia

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In conditions in which the retinal pigment epithelium (RPE) is dystrophic, carries a genetic mutation, or is removed physically, Müller cells undergo degenerative changes that contribute to the retinal pathology. We previously demonstrated that pigment epithelium-derived factor (PEDF), a glycoprotein secreted by the RPE cells with neuroprotective and differentiation properties, protects against photoreceptor degeneration induced by RPE removal. The purpose of the present study was to analyze the putative gliosupportive activity of PEDF on Müller cells of RPE-deprived retinas and assess whether protection of Müller cells was correlated with improved photoreceptor outer segment assembly. Eyes were dissected from Xenopus laevis tadpoles, and the RPE was removed before culturing in medium containing purified PEDF, PEDF plus anti-PEDF, or medium alone. Control eyes matured with an adherent RPE or in medium containing PEDF plus nonimmune serum. Müller cell ultrastructure was examined. Glial fibrillary acidic protein (GFAP) and glutamine synthetase were localized immunocytochemically, and the corresponding protein levels were quantified. In control retinas, Müller cells were structurally intact and formed adherens junctions with neighboring photoreceptors. In addition, they did not express GFAP, whereas glutamine synthetase expression was high. RPE removal dramatically altered the ultrastructure and biosynthetic activity of Müller cells; Müller cells failed to form adherens junctions with photoreceptors and glutamine synthetase expression was suppressed. PEDF prevented the degenerative glial response; Müller cells were ultrastructurally normal and formed junctional complexes with photoreceptors. PEDF also preserved the expression of glutamine synthetase at near-normal levels. The morphogenetic effects of PEDF were blocked by the anti-PEDF antibody. Our study documents the glioprotective effects of PEDF and suggests that maintenance of the proper Müller cell ultrastructure and expression of glutamine synthetase may be necessary to support the proper assembly of photoreceptor outer segments.

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RPE secreted proteins and antibody influence photoreceptor cell survival and maturation

Cited by 35 publications

References 42 publications

RPE-derived factors modulate photoreceptor differentiation: A possible role in the retinal stem cell niche

RPE-derived factors modulate photoreceptor differentiation: A possible role in the retinal stem cell niche

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

Pigment epithelium‐derived factor supports normal Müller cell development and glutamine synthetase expression after removal of the retinal pigment epithelium

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