The lens equator: A platform for molecular machinery that regulates the switch from cell proliferation to differentiation in the vertebrate lens

Abstract

The vertebrate lens is a transparent, spheroidal tissue, located in the anterior region of the eye that focuses visual images on the retina. During development, surface ectoderm associated with the neural retina invaginates to form the lens vesicle. Cells in the posterior half of the lens vesicle differentiate into primary lens fiber cells, which form the lens fiber core, while cells in the anterior half maintain a proliferative state as a monolayer lens epithelium. After formation of the primary fiber core, lens epithelial cells start to differentiate into lens fiber cells at the interface between the lens epithelium and the primary lens fiber core, which is called the equator. Differentiating lens fiber cells elongate and cover the old lens fiber core, resulting in growth of the lens during development. Thus, lens fiber differentiation is spatially regulated and the equator functions as a platform that regulates the switch from cell proliferation to cell differentiation. Since the 1970s, the mechanism underlying lens fiber cell differentiation has been intensively studied, and several regulatory factors that regulate lens fiber cell differentiation have been identified. In this review, we focus on the lens equator, where these regulatory factors crosstalk and cooperate to regulate lens fiber differentiation. Normally, lens epithelial cells must pass through the equator to start lens fiber differentiation. However, there are reports that when the lens epithelium structure is collapsed, lens fiber cell differentiation occurs without passing the equator. We also discuss a possible mechanism that represses lens fiber cell differentiation in lens epithelium.

The cause and consequence of fiber cell compaction in the vertebrate lens

“…At the lens equator, epithelial cells withdraw from the cell cycle, become aligned in meridional rows, and begin the process of fiber cell differentiation (Mochizuki and Masai, 2014). Fiber differentiation is characterized most obviously by an enormous increase in cell length (to values approaching 2 cm in the large bovine lens (Kuszak et al, 2004)).…”

Biophysical chemistry of the ageing eye lens

“…The lens epithelial cells are the only part of the lens that has metabolic activity (Dahm et al 2011). New cells develop from the epithelial layer via mitosis from which they then differentiate into fibre cells (Mochizuki and Masai 2014). As the new fibre cells develop, they express large amounts of crystallin proteins which are responsible for the refractive index and transparency of the lens (Aarts et al 1989;Zhao et al 2011).…”

“…As the new fibre cells develop, they express large amounts of crystallin proteins which are responsible for the refractive index and transparency of the lens (Aarts et al 1989;Zhao et al 2011). Newly differentiated fibre cells migrate towards the lens equator where they undergo denucleation and lose their internal sub-cellular structures (Bassnett 2002;Mochizuki and Masai 2014). The fibre cells ultimately form multiple layers stacked around the central nucleus of the lens.…”

“…When a fibre cell differentiates from the epithelial layer, it express crystallin proteins in high concentration and then undergoes degradation of all organelles and large cell structures. The bulk of the eye lens has no blood supply, no cellular structures such as mitochondria, nucleus, or ribosome, and exhibits no metabolic activity (Dahm et al 2011;Mochizuki and Masai 2014). While this lack of organelle-like sub-structure means the lens fibre cells have exceptional optical properties, it also means that once they have matured they have very little capacity to recycle or repair damaged proteins and no capacity to express new protein (Bloemendal et al 2004;Wang et al 2004).…”

Transcriptome analysis of the zebrafishatoh7−/−mutant,lakritz, highlights Atoh7-dependent genetic networks with potential implications for human eye diseases

“…The rapidly and externally developing transparent zebrafish embryos are amenable to easy genetic manipulation, thus allowing fast generation and identification of mutants modelling human ocular genetic disorders [58][59][60][61][62][63][64] . Such disease models can be concurrently investigated in large-scale genetics, drug screening, in vivo cell biology of early disease development as well as behavioural assays [65][66][67][68] . These potentials substantially aid fast progress in the validation of human genome association studies and in preclinical therapy development paths towards the early diagnosis and/or restoration of visual function [69][70][71][72] .…”