The lens regenerative competency of limbal vs. central regions of mature Xenopus cornea epithelium

Abstract

The frog, Xenopus laevis, is capable of completely regenerating a lens from the cornea epithelium. Because this ability appears to be limited to the larval stages of Xenopus, virtually all the work to understand the mechanisms regulating this process has been limited to pre-metamorphic tadpoles. It has been reported that the post-metamorphic cornea is competent to regenerate under experimental conditions, despite the fact that the in vivo capacity to regenerate is lost; however, that work didn’t examine the regenerative potential of different regions of the cornea. A new model suggests that cornea-lens regeneration in Xenopus may be driven by oligopotent stem cells, and not by transdifferentiation of mature cornea cells. We investigated the regenerative potential of the limbal region in post-metamorphic cornea, where the stem cells of the cornea are thought to reside. Using EdU (5-Ethynyl-2’-deoxyuridine), we identified long-term label retaining cells in the basal cells of peripheral post-metamorphic Xenopus cornea, consistent with slow-cycling stem cells of the limbus that have been described in other vertebrates. Using this data to identify putative stem cells of the limbal region in Xenopus, we tested the regenerative competency of limbal regions and central cornea. All three regions showed a similarly high ability for the cells of the basal epithelium to express lens proteins when cultured in proximity to larval retina. Thus, the regenerative competency in post-metamorphic cornea is not restricted to stem cells of the limbal region, but also occurs in the transit amplifying cells throughout the basal layer of the cornea epithelium.

Lens regeneration: a historical perspective

“…Nevertheless, adult frogs in vivo are unable to regenerate whole lenses except when the lens capsule is left intact and lens epithelial cells attached to it provide a source for re-growth, as is the case in mammals (see next section; Call et al, 2004; Yoshii et al, 2007; Lin et al, 2016). However, Hamilton and Henry (2016) have recently shown that post-metamorphic corneal in vitro explants can initiate the formation of lens cells via the activation of limbal stem cells and transit amplifying cells of the cornea.…”

Expression of stem cell factors in the adult sea cucumber digestive tube

“…The long chase period, on the other hand, provides an insight into how long the newly generated progeny of the dividing cells persist in the tissue. This approach identifies “label-retaining cells” that are capable of surviving for extended periods of time after having undergone cell division and are either post-mitotic or divide infrequently (Hamilton and Henry, 2016). …”

Understanding cornea epithelial stem cells and stem cell deficiency: Lessons learned using vertebrate model systems

“…These differences may be related to the species being studied or the developmental age of the tissues that were examined. Studies reveal that putative CESCs are present throughout the cornea during early development, being more highly restricted to the periphery at later developmental stages (Davies et al, 2009;Hamilton & Henry, 2016;Pajoohesh-Ganji, Ghosh, & Stepp, 2004). Some insight into the role of the surrounding cellular niche was gained when rabbit cornea epithelial cells were recombined with mouse embryonic dermis.…”