The pigmented epithelium sustains cell growth and tissue differentiation of chicken retinal explants in vitro

Liu, Li; Cheng, Song-Hua; Jiang, Lizheng; Hansmann, Gerald; Layer, Paul G.

doi:10.1016/s0014-4835(88)80065-4

Cited by 28 publications

(9 citation statements)

References 35 publications

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“…We therefore investigated whether the RPE increases the rate of cell proliferation. This was likely, since in an explant study and in monolayer cultures the RPE has been shown to strongly support cell proliferation (Liu et al, 1988;Gaur et aL, 1992;Sheedlo et al, 1995). Here, BrdU labelling studies indeed revealed that cell division in the presence of RPE is much higher and the proliferative period outer rim (Fig.…”

Section: Rpe As a General Regulator Of Cell Proliferation And Differesupporting

confidence: 51%

“…Explant cultures or reaggregation experiments provide models to study the behaviour of retinal cells within developing three-dimensional tissue networks (Moscona, 1952;Fujisawa, 1973;Vollmer et al, 1984;Araki, 1984;Akagawa etal., 1987;Watanabe and Raff, 1992; for reviews see Willbold, 1993, 1994). When retinal explants of the chick embryo were cultured with or without their WE, the RPE was found to sustain cell growth and retinal differentiation (Liu et al, 1988). In particular, in the presence of the RPE the rate of cell proliferation and the size of the retinal tissue increased while in its absence neurite outgrowth was more pronounced.…”

Section: Introductionmentioning

confidence: 99%

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Pigmented Epithelium Sustains Cell Proliferation and Decreases Expression of Opsins and Acetylcholinesterase in Reaggregated Chicken Retinospheroids

Layer

Rothermel

Hering

et al. 1997

Eur J of Neuroscience

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We investigated the effect of the retinal pigmented epithelium on cell proliferation and differentiation in rosetted retinospheroids, which are retina-like spheres reaggregated in the complete absence of retinal pigmented epithelium from dissociated retinal cells of 6-day-old chick embryos in a rotation culture system. In spheroids raised in the absence of retinal pigmented epithelium (controls), acetylcholinesterase was expressed in cells of an inner nuclear-like layer and their neuropil matrices. Moreover, the ratio between rods and cones was found to be approximately normal throughout the spheroid. When spheroids were cultured in the presence of retinal pigmented epithelium monolayers, cell proliferation in spheroids as determined by BrdU labelling was significantly increased and extended for 1 week, while acetylcholinesterase protein levels and specific activities in homogenates were decreased to approximately 30%. At the same time, opsin immunoreactivity was completely suppressed within the spheroid and appeared slowly in cells around its periphery; i.e. the proportion of rhodopsin-positive cells decreased from 14 to 3%. This study reveals that the retinal pigmented epithelium in vitro sustains cell proliferation but inhibits the differentiation of acetylcholinesterase-positive cells and of photoreceptors.

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Section: Rpe As a General Regulator Of Cell Proliferation And Differesupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Pigmented Epithelium Sustains Cell Proliferation and Decreases Expression of Opsins and Acetylcholinesterase in Reaggregated Chicken Retinospheroids

Layer

Rothermel

Hering

et al. 1997

Eur J of Neuroscience

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“…For example, cells of a more neural character are induced in retinal cells cocultured with RPE cells (Israel et al, 1978). Similarly, a high level of retinal organization (Volmer et al., 1984) and the maintenance of cell growth and differentiation well as from adult human and monkey secrete PEDE Moreover, of chicken retinal explants (Liu et al, 1988) are reported in PEDF is clearly present in soluble extracts of IPM derived from cultures containing RPE cells. The induction of neuronal differ-the fetal cow as well as from the adult cow and human.…”

Section: Discussionmentioning

confidence: 97%

Expression, secretion, and age-related downregulation of pigment epithelium-derived factor, a serpin with neurotrophic activity

et al. 1995

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Retinal pigment epithelial (RPE) cells form a functional complex with photoreceptor neurons of the retina, interacting through the interphotoreceptor matrix (IPM). We now provide evidence that the gene for pigment epithelium-derived factor (PEDF), a protein possessing neurotrophic and neuronal-survival activities, is highly expressed by both fetal and young adult RPE cells. PEDF mRNA is present in RPE cells of the human eye at 17 weeks of gestation, demonstrating its potential for action in vivo during early retinal development. The PEDF protein is secreted in vivo where it constitutes a part of the fetal and adult IPM surrounding photoreceptor outer segments. A polyclonal PEDF antibody recognizes at least four isoforms of secreted human and bovine PEDF by two dimensional gel analysis, and detects a similar 50 kDa protein in the IPM of several other vertebrate species. Within soluble extracts of RPE cells, however, where little, if any, of the 50 kDa species can be detected, an immunoreactive 36 kDa protein is observed by Western blot analysis. By immunofluorescence, PEDF is localized intracellularly in association with the nucleus, presumptive secretory granules, and cytoskeletal elements of cultured RPE cells with PEDF and actin antibodies colocalizing to the same cytoskeletal structures. During initial stages of attachment, PEDF and actin also concentrate at the tips of pseudopods extended by the cultured RPE cells. However, with successive passages, synthesis, and secretion of the PEDF protein as well as transcription of its mRNA decrease and are lost by about 10 passages. In parallel, cultured RPE cells lose their proliferative potential and change from an epithelial-like morphology in early passages to a more fibroblast-like appearance by about the 10th passage. PEDF is thus apparently present intracellularly and extracellularly in both fetal and early adult periods where it could be involved in cellular differentiation and survival and with its loss, in the onset of senescence.

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“…Known signals that may be involved in coordinating retinal cell proliferation, commitment, and differentiation include several growth factors/cytokines (Anchan et al, 1991;Guillemot and Cepko, 1992;Lillien and Cepko, 1992;Tcheng et al, 1994;Anchan and Reh, 1995), retinoids (Stenkamp et al, 1993;Kelley et al, 1994Kelley et al, , 1995Hyatt et al, 1996a,b), and neurotransmitters (Pow et al, 1994;Redburn and Rowe-Rendleman, 1996). Additionally, factors derived from the subretinal space, or from the retinal pigmented epithelium (RPE), have been described as having one or more of these effects, but most of these factors have not been conclusively identified (Liu et al, 1988;Spoerri et al, 1988;Hewitt et al, 1990;Watanabe and Raff, 1992;Steele et al, 1993;Sheedlo and Turner, 1996). It is therefore likely that many of the signaling molecules involved in the regulation of retinal cell differentiation remain undescribed.…”

Section: Introductionmentioning

confidence: 99%

Function for Hedgehog Genes in Zebrafish Retinal Development

Stenkamp

Frey

Prabhudesai

et al. 2000

Developmental Biology

147

122

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The hedgehog (hh) genes encode secreted signaling proteins that have important developmental functions in vertebrates and invertebrates. In Drosophila, expression of hh coordinates retinal development by propagating a wave of photoreceptor differentiation across the eye primordium. Here we report that two vertebrate hh genes, sonic hedgehog (shh) and tiggy-winkle hedgehog (twhh), may perform similar functions in the developing zebrafish. Both shh and twhh are expressed in the embryonic zebrafish retinal pigmented epithelium (RPE), initially in a discrete ventral patch which then expands outward in advance of an expanding wave of photoreceptor recruitment in the subjacent neural retina. A gene encoding a receptor for the hedgehog protein, ptc-2, is expressed by retinal neuroepithelial cells. Injection of a cocktail of antisense (alphashh/alphatwhh) oligonucleotides reduces expression of both hh genes in the RPE and slows or arrests the progression of rod and cone photoreceptor differentiation. Zebrafish strains known to have mutations in Hh signaling pathway genes similarly exhibit retardation of photoreceptor differentiation. We propose that hedgehog genes may play a role in propagating photoreceptor differentiation across the developing eye of the zebrafish.

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The pigmented epithelium sustains cell growth and tissue differentiation of chicken retinal explants in vitro

Cited by 28 publications

References 35 publications

Pigmented Epithelium Sustains Cell Proliferation and Decreases Expression of Opsins and Acetylcholinesterase in Reaggregated Chicken Retinospheroids

Pigmented Epithelium Sustains Cell Proliferation and Decreases Expression of Opsins and Acetylcholinesterase in Reaggregated Chicken Retinospheroids

Expression, secretion, and age-related downregulation of pigment epithelium-derived factor, a serpin with neurotrophic activity

Function for Hedgehog Genes in Zebrafish Retinal Development

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