Lens stem cells may reside outside the lens capsule: an hypothesis

Historically, the lens has been viewed as a closed system, in which cells at the periphery of the lens epithelium differentiate into fiber cells. Theoretical considerations led us to question whether the intracapsular lens is indeed self-contained. Since stem cells generate tumors and the lens does not naturally develop tumors, we reasoned that lens stem cells may not be present within the capsule. We hypothesize that lens stem cells reside outside the lens capsule, in the nearby ciliary body. Our ideas challenge the existing lens biology paradigm.We begin our discussion with lens background information, in order to describe our lens stem cell hypothesis in the context of published data. Then we present the ciliary body as a possible source for lens stem cells, and conclude by comparing the ocular lens with the corneal epithelium.The vertebrate lens is a transparent cellular structure, specialized to focus and transmit light. The lens is composed of two cell types – epithelial cells that form a single cuboidal layer on the anterior surface, and elongated fiber cells that form the posterior bulk of the lens (Figure 1). A capsule of extracellular matrix components encompasses the lens.The lens grows slowly throughout life, primarily via cell division in the germinative zone. The germinative zone is a narrow cellular region that rings the lens epithelium toward the periphery of the anterior lens surface. Newly formed cells within the germinative zone elongate and migrate along the inner capsular surface toward the lens equator, forming new lens fiber cells as they continue to elongate and migrate posteriorly beyond the equator. These new fiber cells add to the periphery of the existing fiber cell mass, displacing older fiber cells toward the interior of the expanding lens [1-3]. Central fiber cells are retained for life. Historically, the adult lens has been viewed as a closed system, in which all lens precursor cells or stem cells reside within the capsular confines.W