Held under arrest: Many mature albino RPE cells display polyploidal features consistent with abnormal cell cycle retention

Adams, Tom; Shahabi, Golnaz; Hoh-Kam, Jaimie; Jeffery, Glen

doi:10.1016/j.exer.2009.10.002

Cited by 14 publications

(24 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also the morphology of their RPE cells becomes progressively abnormal due to the development of polyploidy (Adams et al, 2010 ). Interestingly, in light of this, Penn and Williams ( 1986 ) stated that "The albino rat has been questioned as a model for retinal research in the past…" Also they concluded that "It is possible, perhaps, that photostasis may be an anomalous phenomenon, applicable only to the albino rat."…”

Section: Discussionmentioning

confidence: 96%

Questioning photostasis

et al. 2013

Self Cite

View full text Add to dashboard Cite

Photostasis is a phenomenon where the photoreceptor outer segment (OS) length and its rhodopsin content vary depending on environmental lighting. When light is reduced for extended periods, it is argued that OS lengthen and its rhodopsin concentration rises to increase photon capture in darker environment. Increases in OS length may occur because the retinal pigment epithelium (RPE) cells reduce OS consumption in prolonged darkness. But sample sizes in assessing changes in OS length have been small, and results highly varied with no statistical analysis ever offered. Further, animals used were often albinos, which have abnormal RPE cells. Here we keep pigmented and albino mice for 21 days in darkness and compare OS length with those in a normal 12:12 light/dark environment. We measured approximately 1300 OS but found no statistically significant difference in their lengths between light and dark groups in either pigmentation phenotype, although there was a small trend in the data favoring OS extension in the dark. Given that earlier studies were undertaken on limited samples with no statistical analysis, our data pose serious questions for the notion of mammalian photostasis in terms of significant OS plasticity.

show abstract

Section: Discussionmentioning

confidence: 96%

Questioning photostasis

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…On day 7 in vitro, cells were pulse-labelled with BrdU (0.5 µM) and 1 µl (4 M) NaOH in DMEM-F12+Glutamax for 4 hours. Incorporation of BrdU in vivo during S-phase was used as described previously [8].…”

Section: Methodsmentioning

confidence: 99%

“…The far periphery is also thought to be a region from which stem cells can be harvested in the adult [7]. Mature peripheral RPE cells retain an ability to divide throughout life and some migrate into central senescent regions [8], [9]. Here we ask whether these peripheral cells have an intrinsic capacity to divide, marking them as distinct, or whether this ability is related to their local microenvironment and/or its signals.…”

Section: Introductionmentioning

confidence: 99%

Mature Peripheral RPE Cells Have an Intrinsic Capacity to Proliferate; A Potential Regulatory Mechanism for Age-Related Cell Loss

et al. 2011

Self Cite

View full text Add to dashboard Cite

BackgroundMammalian peripheral retinal pigmented epithelium (RPE) cells proliferate throughout life, while central cells are senescent. It is thought that some peripheral cells migrate centrally to correct age-related central RPE loss.Methodology/Principal FindingsWe ask whether this proliferative capacity is intrinsic to such cells and whether cells located centrally produce diffusible signals imposing senescence upon the former once migrated. We also ask whether there are regional differences in expression patterns of key genes involved in these features between the centre and the periphery in vivo and in vitro. Low density RPE cultures obtained from adult mice revealed significantly greater levels of proliferation when derived from peripheral compared to central tissue, but this significance declined with increasing culture density. Further, exposure to centrally conditioned media had no influence on proliferation in peripheral RPE cell cultures at the concentrations examined. Central cells expressed significantly higher levels of E-Cadherin revealing a tighter cell adhesion than in the peripheral regions. Fluorescence-labelled staining for E-Cadherin, F-actin and ZO-1 in vivo revealed different patterns with significantly increased expression on central RPE cells than those in the periphery or differences in junctional morphology. A range of other genes were investigated both in vivo and in vitro associated with RPE proliferation in order to identify gene expression differences between the centre and the periphery. Specifically, the cell cycle inhibitor p27Kip1 was significantly elevated in central senescent regions in vivo and mTOR, associated with RPE cell senescence, was significantly elevated in the centre in comparison to the periphery.ConclusionsThese data show that the proliferative capacity of peripheral RPE cells is intrinsic and cell-autonomous in adult mice. These differences between centre and periphery are reflected in distinct patterns in junctional markers. The regional proliferation differences may be inversely dependent to cell-cell contact.

show abstract

“…Therefore, neuronal cell injury, of the type that occurs in neurodegenerative diseases such as retinitis pigmentosa or age-related macular degeneration, usually results in irreversible vision loss 6, 7 . However, there is evidence that despite being largely post-mitotic, some mature RPE cells continue to divide 8, 9 mostly in the peripheral retina 10 , as well as during pathological complications following retinal detachment that lead to proliferative vitreoretinopathy 11 . In contrast, when cultured ex vivo , RPE cells can be highly proliferative, though this is usually accompanied by substantial de-differentiation manifested as loss of pigment granules, cell polarity and expression of key RPE cell genes such as RPE65 and the Mer tyrosine kinase.…”

Section: Introductionmentioning

confidence: 99%

Regulation of retinal pigment epithelial cell phenotype by Annexin A8

Lueck¹,

Carr²,

Stampoulis³

et al. 2017

Sci Rep

View full text Add to dashboard Cite

The retinoic acid derivative fenretinide (FR) is capable of transdifferentiating cultured retinal pigment epithelial (RPE) cells towards a neuronal-like phenotype, but the underlying mechanisms are not understood. To identify genes involved in this process we performed a microarray analysis of RPE cells pre- and post-FR treatment, and observed a marked down-regulation of AnnexinA8 (AnxA8) in transdifferentiated cells. To determine whether AnxA8 plays a role in maintaining RPE cell phenotype we directly manipulated AnxA8 expression in cultured and primary RPE cells using siRNA-mediated gene suppression, and over-expression of AnxA8-GFP in conjunction with exposure to FR. Treatment of RPE cells with AnxA8 siRNA recapitulated exposure to FR, with cell cycle arrest, neuronal transdifferentiation, and concomitant up-regulation of the neuronal markers calretinin and calbindin, as assessed by real-time PCR and immunofluorescence. In contrast, AnxA8 transient over-expression in ARPE-19 cells prevented FR-induced differentiation. Ectopic expression of AnxA8 in AnxA8-depleted cells led to decreased neuronal marker staining, and normal cell growth as judged by phosphohistone H3 staining, cell counting and cleaved caspase-3 levels. These data show that down-regulation of AnxA8 is both necessary and sufficient for neuronal transdifferentiation of RPE cells and reveal an essential role for AnxA8 as a key regulator of RPE phenotype.

show abstract

Held under arrest: Many mature albino RPE cells display polyploidal features consistent with abnormal cell cycle retention

Cited by 14 publications

References 11 publications

Questioning photostasis

Questioning photostasis

Mature Peripheral RPE Cells Have an Intrinsic Capacity to Proliferate; A Potential Regulatory Mechanism for Age-Related Cell Loss

Regulation of retinal pigment epithelial cell phenotype by Annexin A8

Contact Info

Product

Resources

About