Genetic basis of corneal diseases and the role of keratocytes in corneal transparency – a review

Abstract

AbstractThe current paper reviews the genetic basis of diseases affecting the cornea, including corneal dystrophies and systemic diseases with corneal manifestations (e.g. the mucopolysaccharidoses), discusses the mechanisms by which corneal injury and disease can affect corneal transparency and discusses stem cell therapy as a potential therapy for corneal injury and disease. Several diseases of the cornea have been described, many of which are inheritable. The identification of the genetic mutations responsible for these diseases has led to a better understanding of the mechanisms underlying their corneal manifestations. Corneal disease and injury can affect corneal transparency. Stromal keratocytes play an important role in cellular and extracellular transparency of the cornea. They synthesize type I and V collagen and keratan sulfate proteoglycans that together regulate collagen fibril size and spacing important for extracellular matrix transparency. There are strong indications that cellular transparency of keratocytes relies on the presence of corneal crystallins, which provide a uniform density of proteins in the cytoplasm that increase the spatial order necessary for transparency. After injury, activated keratocytes show heterogeneity of cytoplasmic proteins, decreased spatial ordering and increased light scattering. Stem cell transplantation is regarded as a potential new therapy that can replace keratocytes and restore corneal transparency and normal structure after injury or corneal disease.