The T-Box Transcription Factor TBX2 Regulates Cell Proliferation in the Retinal Pigment Epithelium

2017 ◽  
Vol 42 (11) ◽  
pp. 1537-1544 ◽  
Author(s):  
Jing Wang ◽  
Yin Liu ◽  
Zhongyuan Su ◽  
Li Pan ◽  
Fan Lu ◽  
...  
1995 ◽  
Vol 73 (9-10) ◽  
pp. 709-722 ◽  
Author(s):  
Vitauts. I. Kalnins ◽  
Martin Sandig ◽  
Greg J. Hergott ◽  
Haruhiko Nagai

Several systems of microfilaments (MF) associated with adherens-type junctions between adjacent retinal pigment epithelial (RPE) cells and between these cells and the substratum play an important role in maintaining the integrity and organization of the RPE. They include prominent, contractile circumferential MF bundles that are associated with the zonula adherens (ZA) junctions. In chick RPE, these junctions are assembled from smaller subunits thus giving greater structural flexibility to the junctional region. Because the separation of the junctions requires trypsin and low calcium, both calcium-dependent and -independent mechanisms are involved in keeping adjacent RPE cells attached to one another. Another system of MF bundles that crosses the cell at the level of ZA junctions can be induced to form by stretching the epithelium. The MF bundles forming this system are oriented in the direction in which the RPE is stretched, thereby preventing the overextension of the cell in any one direction. The system may be useful as an indicator of the direction in which tension is experienced by RPE during development of the eye, in animal models of disease and during repair of experimentally induced wounds. Numerous single-cell wounds resulting from death of RPE cells by apoptosis at various stages of repair are normally present in developing chick and adult mammalian RPE. These wounds are repaired by the spreading of adjacent RPE cells and by the contraction of MF bundles oriented parallel to the wound edge, which develop during this time. As a result of the spreading in the absence of cell proliferation, the RPE cells increase in diameter with age. Experimentally induced wounds made by removing 5–10 RPE cells are repaired by a similar mechanism within 24 h. In repair of larger wounds, over 125 μm in width, the MF bundles oriented parallel to the wound edge characteristic of spreading cells are later replaced by stress fibers (SFs) that run perpendicularly to the wound edge and interact with the substratum at focal contacts (FCs) as RPE cells start to migrate. Cell proliferation is induced in cells along the wound edge only when the wounds are wide enough to require cell migration. In the presence of antibodies to beta-1-integrins, a component of FCs, cell spreading is not prevented but both cell migration and cell proliferation are inhibited. Thus, only the organization of the cytoskeleton characteristic of migrating RPE cells that have SFs that interact with the substratum at FCs, is associated with the induction of cell proliferation.Key words: retinal pigment epithelium, microfilaments, wound repair.


Development ◽  
1999 ◽  
Vol 126 (17) ◽  
pp. 3757-3767 ◽  
Author(s):  
J.A. Lister ◽  
C.P. Robertson ◽  
T. Lepage ◽  
S.L. Johnson ◽  
D.W. Raible

We report the isolation and identification of a new mutation affecting pigment cell fate in the zebrafish neural crest. Homozygous nacre (nac(w2)) mutants lack melanophores throughout development but have increased numbers of iridophores. The non-crest-derived retinal pigment epithelium is normal, suggesting that the mutation does not affect pigment synthesis per se. Expression of early melanoblast markers is absent in nacre mutants and transplant experiments suggested a cell-autonomous function in melanophores. We show that nac(w2) is a mutation in a zebrafish gene encoding a basic helix-loop-helix/leucine zipper transcription factor related to microphthalmia (Mitf), a gene known to be required for development of eye and crest pigment cells in the mouse. Transient expression of the wild-type nacre gene restored melanophore development in nacre(−/−) embryos. Furthermore, misexpression of nacre induced the formation of ectopic melanized cells and caused defects in eye development in wild-type and mutant embryos. These results demonstrate that melanophore development in fish and mammals shares a dependence on the nacre/Mitf transcription factor, but that proper development of the retinal pigment epithelium in the fish is not nacre-dependent, suggesting an evolutionary divergence in the function of this gene.


2019 ◽  
Author(s):  
Jialin Li ◽  
I-Chen Chao ◽  
Jie Luan

Abstract Background: Hyperbaric oxygen (HBO) therapy has been widely used in various diseases, which is considered safe and effective. Whereas recent studies discovered that HBO therapy could result in oxidative damage to tissues. The goal of our study was to investigate the oxidative effect of hyperbaric oxygen therapy on human retinal pigment epithelium (RPE) cells. Method: Human REP cells (ARPE-19) were cultured in vitro, and divided into normoxic group (incubated with DMEM/F12 broth)and hypoxic group (incubated with DMEM/F12 broth containing 200μmol/L CoCl2) randomly. The experimental groups were exposed to 100% pure oxygen under different pressures (0.15MPa, 0.2MPa, and 0.25MPa) for 60 and 90 minutes thrice, with 24 hours interval. Then the cell viability, 8-OHdG expression and hOGG1 expression of RPE cells were detected by MTT assay, immunocytochemistry (ICC) and western blot seperately. Result: After HBO exposure, cell proliferation decreased, 8-OHdG and hOGG1 expression increased in normoxic RPE cells compared with control group, whereas in hypoxic RPE cells, cell proliferation increased, 8-OHdG and hOGG1 expression decreased compared with hypoxic control group. Conclusion: HBO therapy could suppress the cell proliferation and cause oxidative DNA damage of RPE cells in normoxic status. Conversely, in hypoxic status, HBO therapy could promote the proliferation and ameliorate oxidative DNA damage of human retinal pigment epithelium cells. Meanwhile, HBO therapy could trigger the oxidative DNA damage repair of RPE cells in both normoxic and hypoxic statues.


1998 ◽  
Vol 247 (3) ◽  
pp. 710-715 ◽  
Author(s):  
Shintaro Amae ◽  
Nobuo Fuse ◽  
Ken-ichi Yasumoto ◽  
Shigeru Sato ◽  
Ichiro Yajima ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Xinrong Xu ◽  
Li Hang ◽  
Binglin Huang ◽  
Yuanhua Wei ◽  
Shizhong Zheng ◽  
...  

Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a large role in the pathogenesis of AMD. The present study was to evaluate the effects ofFructus lyciiethanol extract on AMD in mice and to investigate whether combination of lutein and zeaxanthin, two carotenoid pigments inFructus lycii, could protect human retinal pigment epithelial ARPE-19 cells treated with hydrogen peroxide (H2O2)in vitro. We found that severe sediment beneath retinal pigment epithelium and thickened Bruch membrane occurred in AMD mice. However,Fructus lyciiethanol extract improved the histopathologic changes and decreased the thickness of Bruch membrane. Furthermore, the gene and protein expression of cathepsin B and cystatin C was upregulated in AMD mice but was eliminated byFructus lyciiethanol extract. Investigationsin vitroshowed that ARPE-19 cell proliferation was suppressed by H2O2. However, lutein/zeaxanthin not only stimulated cell proliferation but also abrogated the enhanced expression of MMP-2 and TIMP-1 in H2O2-treated ARPE-19 cells. These data collectively suggested thatFructus lyciiethanol extract and its active components lutein/zeaxanthin had protective effects on AMDin vivoandin vitro, providing novel insights into the beneficial role ofFructus lyciifor AMD therapy.


1994 ◽  
Vol 26 (5) ◽  
pp. 304-309 ◽  
Author(s):  
Daniel Mojon ◽  
Daniel Boscoboinik ◽  
Anita Haas ◽  
Matthias Bohnke ◽  
Angelo Azzi

2019 ◽  
Author(s):  
Sally H. Cross ◽  
Lisa Mckie ◽  
Toby W. Hurd ◽  
Sam Riley ◽  
Jimi Wills ◽  
...  

AbstractThe precise control of eye size is essential for normal vision. TMEM98 is a highly conserved and widely expressed gene which appears to be involved in eye size regulation. Mutations in human TMEM98 are found in patients with nanophthalmos (very small eyes) and variants near the gene are associated in population studies with myopia and increased eye size. As complete loss of function mutations in mouse Tmem98 result in perinatal lethality, we produced mice deficient for Tmem98 in the retinal pigment epithelium (RPE), where Tmem98 is highly expressed. These mice have greatly enlarged eyes that are very fragile with very thin retinas. To gain insight into the mechanism of action we used a proximity labelling approach to discover interacting proteins and identified MYRF as an interacting partner. Mutations of MYRF are also associated with nanophthalmos. The protein is an endoplasmic reticulum-tethered transcription factor which undergoes autoproteolytic cleavage to liberate the N-terminal part which then translocates to the nucleus where it acts as a transcription factor. We find that TMEM98 inhibits the self-cleavage of MYRF, in a novel regulatory mechanism. In RPE lacking TMEM98, MYRF is ectopically activated and abnormally localised to the nuclei.Author summaryHaving the correct eye size is important, too large and you will be short-sighted and too small and you will be far-sighted. Nanophthalmos, literally very small eye from the Greek, is a condition where the eye is very small but structurally normal. In addition to being farsighted such eyes are prone to glaucoma which can lead to loss of vision. Here we studied a protein called TMEM98 which is found in the membranes of the cells which form a layer at the back of eye called the retinal pigment epithelium (RPE). Mutations in TMEM98 have been found in nanophthalmos patients. Patients have one normal copy of the gene and one carrying a mutation. We removed Tmem98 from the RPE of mice in order to ascertain its function. We found, surprisingly, that rather than having small eyes this led to the development of very large eyes that were structurally fragile. We went to on to identify protein partners of TMEM98 and found that it interacts with a protein called MYRF, mutations in which also causes nanophthalmos. This work demonstrates the importance of TMEM98 in eye size specification.


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