Mammals Have Some Capacity for Lens Regeneration

Rabbits, cats, and mice can regenerate an imperfect lens if the lens is removed from the lens capsule, leaving the capsule behind (Gwon et al., 1990; Call et al., 2004). A new lens is formed by the proliferation and differentiation of residual lens epithelium cells that remain adherent to the lens capsule. Interestingly, in human cataract surgery to replace the lens with a plastic lens, the posterior, and part of the anterior, lens capsule is left behind to hold the artificial lens. Residual lens epithelial cells adhering to the anterior part of the capsule sometimes undergo an epithelial to mesenchymal transformation and proliferate across the whole posterior lens surface, where they essentially form new cataracts, a process called posterior capsule opacification (PCO) (Wormstone et al., 2001). In these cases, the surgeon uses a laser to ablate the proliferating cells and the posterior capsule. PCO happens in other mammals as well, but is diminished considerably by 20 days postlen-tectomy (Call et al., 2004).

If residual lens epithelial cells in human lens capsules could be directed to proliferate and differentiate into proper lens fibers, it might be possible to simply regenerate a lens, rather than implant an artificial one. A culture system to explore this possibility has been devised in which residual lens epithelial cells proliferate within the capsules (Wormstone et al., 2001). FGF-2, FGFR1, Pax-6, and Six-3 have been shown to be expressed in these cultures. Inhibition of FGFR1 by the specific antagonist SU5402 retarded proliferation of the epithelial cells.

Mammals do not regenerate a lens from PECs of the dorsal iris. Neverthless, mammalian PECs have the ability to form lenses under the right conditions. Cells of the human H80HrPE-6 dedifferentiated PEC line, derived from an 80-year-old man, formed clear lentoid-like aggregates that expressed crystallins after four days of culture on Matrigel (Eguchi, 1998; Tsonis et al., 2001). Thus, if all the factors involved in lens regeneration from the dorsal iris in newts become known, it may be possible to intervene to regenerate a lens from the dorsal iris in humans.

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