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Toll-like receptor 4 restricts retinal progenitor cell proliferation

¹ Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel
² Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA 02114

Correspondence to Michal Schwartz: michal.schwartz{at}weizmann.ac.il

Retinal neurogenesis ceases by the early postnatal period, although retinal progenitor cells (RPCs) persist throughout life. In this study, we show that in the mammalian eye, the function of Toll-like receptor 4 (TLR4) extends beyond regulation of the innate immune response; it restricts RPC proliferation. In TLR4-deficient mice, enhanced proliferation of cells reminiscent of RPCs is evident during the early postnatal period. In vitro experiments demonstrate that TLR4 acts as an intrinsic regulator of RPC fate decision. Increased TLR4 expression in the eye correlates with the postnatal cessation of cell proliferation. However, deficient TLR4 expression is not sufficient to extend the proliferative period but rather contributes to resumption of proliferation in combination with growth factors. Proliferation in vivo is inhibited by both MyD88-dependent and -independent pathways, similar to the mechanisms activated by TLR4 in immune cells. Thus, our study attributes a novel role to TLR4 as a negative regulator of RPC proliferation.

Abbreviations used in this paper: ANOVA, analysis of variance; βIIIT, βIII-tubulin; CE, ciliary epithelium; CNS, central nervous system; DCX, doublecortin; GF, growth factor; PN, postnatal day; RPC, retinal progenitor cell; TLR, Toll-like receptor; TLR4D, TLR4 deficient; upLPS, ultrapurified lipopolysaccharide; WT, wild type.

© 2008 Shechter et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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This article has been cited by other articles:

• Shechter, R., Ronen, A., Rolls, A., London, A., Bakalash, S., Young, M. J., Schwartz, M. (2008). Toll-like receptor 4 restricts retinal progenitor cell proliferation. JEM 205: i26-i26 [Full Text]  

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