Lens regeneration in humans: using regenerative potential for tissue repairing

Abstract

The crystalline lens is an important optic element in human eyes. It is transparent and biconvex, refracting light and accommodating to form a clear retinal image. The lens originates from the embryonic ectoderm. The epithelial cells at the lens equator proliferate, elongate and differentiate into highly aligned lens fiber cells, which are the structural basis for maintaining the transparency of the lens. Cataract refers to the opacity of the lens. Currently, the treatment of cataract is to remove the opaque lens and implant an intraocular lens (IOL). This strategy is inappropriate for children younger than 2 years, because a developing eyeball is prone to have severe complications such as inflammatory proliferation and secondary glaucoma. On the other hand, the absence of the crystalline lens greatly affects visual function rehabilitation. The researchers found that mammalian lenses possess regenerative potential. We identified lens stem cells through linear tracking experiments and designed a minimally invasive lens-content removal surgery (MILS) to remove the opaque lens material while preserving the lens capsule, stem cells and microenvironment. In infants with congenital cataract, functional lens regeneration in situ can be observed after MILS, and the prognosis of visual function is better than that of traditional surgery. Because of insufficient regenerative ability in humans, the morphology and volume of the regenerated lens cannot reach the level of a normal lens. The activation, proliferation and differentiation of lens stem cells and the alignment of lens fibers are regulated by epigenetic factors, growth factors, transcription factors, immune system and other signals and their interactions. The construction of appropriate microenvironment can accelerate lens regeneration and improve its morphology. The therapeutic concept of MILS combined with microenvironment manipulation to activate endogenous stem cells for functional regeneration of organs in situ can be extended to other tissues and organs with strong self-renewal and repair ability.