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Growth Factor Signaling in Lens Fiber Differentiation

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Lens Epithelium and Posterior Capsular Opacification

Abstract

Since the first reports of experimental lens inversion causing changes in lens cell fate in the 1960s, various factors including the mitogens IGF, EGF, PDGF, as well as Wnts, Notch, and BMPs have been implicated in the regulation of lens fiber cell differentiation, although the preponderance of evidence suggests that FGFs provide the major signal for this process. It is becoming increasingly apparent that complex interactions between the signaling pathways activated by these factors are required to generate functional fiber cells. Disruption of these signaling cascades usually results in the formation of congenital lens defects, including cataracts, and it is likely that these signaling cascades also regulate lens “regenerative” processes that follow extracapsular cataract extraction and lead to Soemmering’s ring and Elschnig’s pearls. Improved knowledge of the signaling processes that occur in normal lens development as well as in the lens epithelial cells (LECs) remaining in the capsular bag following cataract surgery may not only improve the outcomes of cataract treatment but may also eventually lead to the capacity to regenerate functional lenses either from “induced pluripotent stem cells” or from the patient’s own remnant LECs.

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Abbreviations

BMP:

Bone morphogenetic protein

Dvl:

Dishevelled

EGF:

Epidermal growth factor

EMT:

Epithelial–mesenchymal transition

ERK:

Extracellular-regulated kinase

FGF:

Fibroblast growth factor

FGFR:

Fibroblast growth factor receptor

Fzd:

Frizzled

HSPG:

Heparan sulfate proteoglycan

IGF:

Insulin-like growth factor

JAK:

Janus kinase

LEC:

Lens epithelial cell

MAPK:

Mitogen-activated protein kinase

NICD:

Notch intracellular domain

PCO:

Posterior capsule opacification

PCP:

Planar cell polarity

PDGF:

Platelet-derived growth factor

PI3K:

Phosphatidylinositol-3-kinase

PLC:

Phospholipase C

STAT:

Signal transducer and activator of transcription

TGF:

Transforming growth factor

TNF:

Tumor necrosis factor

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Authors and Affiliations

  1. Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, VIC, 3010, Australia

    Robb U. de Iongh

  2. Department of Biological Sciences, University of Delaware, Newark, DE, 19716, USA

    Melinda K. Duncan

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  1. Robb U. de Iongh
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Correspondence to Robb U. de Iongh .

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  1. Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Wakayama, Japan

    Shizuya Saika

  2. John A. Moran Eye Center University of Utah, Salt Lake City, Utah, USA

    Liliana Werner

  3. School of Medical Sciences Anatomy & Histology, Lens Research Laboratory The University of Sydney, Sydney, New South Wales, Australia

    Frank J. Lovicu

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de Iongh, R.U., Duncan, M.K. (2014). Growth Factor Signaling in Lens Fiber Differentiation. In: Saika, S., Werner, L., Lovicu, F. (eds) Lens Epithelium and Posterior Capsular Opacification. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54300-8_5

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