Therapeutic strategies in ocular tissue regeneration: The role of stem cells

Abstract

The eye is a unique window providing direct visualization of the structure and function of epithelial, vascular, and neural tissue. It thus serves as an ideal "model" for assessing cell-therapy based regenerative strategies. Loss of ocular tissues through injury and degeneration may result in visual morbidity; therefore, a need to explore possible avenues of cellular regeneration by manipulation of host and embryonic stem cells exists. In the adult eye, stem cells have been identified in various locations including the conjunctiva, corneal limbus, ciliary body, and neural retina. Recent studies have also suggested that bone marrow derived stem cells are recruited in pathological neovascularization involving both the retina and choroid. The aim of this chapter is to translate basic scientific understanding into useful clinical application ensuring that the potential promise of stem cell studies is not "lost in translation" in the journey from laboratory to clinic. Stem cell science underpins regenerative medicine by providing the means to potentially restore the function of pre-existing but under-performing host tissue. It also has the capacity to introduce a completely new viable stem cell pool into the host. Maximizing the potential of both approaches requires a detailed understanding of the stem cell "niche", inter-cellular dialogue, and cell traffic. Maintenance of a newly established stem cell pool also requires insight into pharmacological manipulation of the extracellular matrix and micro-environmental factors. In order to achieve successful tissue regeneration it is necessary to exploit a number of technologies embracing multiple disciplines - molecular and cell biology, gene therapy, tissue engineering, immunotherapy, and sustained-release nanotechnology. In order to appreciate the concept of ocular tissue regeneration, an understanding of applied ocular anatomy is assumed. The eye is formed by the anterior chamber, the cornea, the conjunctiva, and the lens (www.eyeatlas.com/ Eyeatlas/hom.html, www.icaen.uiowa.edu/aip/Lectures/eye-phys-lecture.pdf). The eye is protected by the eyelid and is hosted in the skull orbital chamber. A wide variety of ocular cell types exist - epithelial cells, stromal cells, neurones, photo-receptors, blood vessels, capillaries, immunological cells, and others. Each cell type has a specific role, thus ensuring the process of vision through which light waves from an object penetrate the cornea to progress into the pupil that is the opening in the centre of the iris. In sequence, the light waves are converged towards a so called nodal point by the cornea and by the crystalline lens that is located behind the pupil. At the nodal point, the image is reversed and inverted. After this image transformation, the light progresses through the vitreous humor that is a gelatineous substance that represents approximately 80% of the eye volume. Through the vitreous humor, the light reaches the retina that is located in the eye posterior area. There, the light waves hit themacula that is a small area of the retina that is responsible for transforming the light waves into electrical signals. These signals can be captured by the optic nerve to be conveyed to the brain by the visual 342 K. Ramaesh et al. pathway. Because of their regenerative potential, upon damage, stem cells should be able to proliferate into one or more of the different cell types belonging to each eye tissue. © Springer Science+Business Media, LLC 2009.