Proteoglycans in retina

Abstract

In this article, we summarize the roles of proteoglycans in retinal tissue. Chondroitin sulfate and heparan sulfate proteoglycans are the major constituents in proteoglycans expressed in retinal tissue. Soluble heparan sulfate proteoglycans are found in the extracellular matrices of the basement membrane, such as the inner limiting membrane and Bruch's membrane, whereas heparan sulfate proteoglycans with their membrane-binding domain are localized primarily in the neurites of retinal neuronal cells, indicating their role as receptors for cytokines. The distribution of chondroitin sulfate proteoglycans is classified into two regions: nerve fiber-rich layers such as the optic nerve, inner plexiform layer and outer plexiform layer, and the interphotoreceptor matrix (IPM). The expression in the nerve fiber-rich layers of several chondroitin sulfate proteoglycans, such as neurocan and phosphacan, is restricted in the nervous tissues, and is upregulated as retinal development proceeds, then decreases after maturation of the retina. In vitro data suggest that these proteoglycans regulate axon guidance and synapse formation during the development of nervous tissue. In contrast, in adult vertebrate retina, the IPM is a rich source of chondroitin sulfate proteoglycans. Histologic data from animals with experimental retinitis pigmentosa, and the existence of the hyaluronan-binding domain in their core proteins, indicate that these proteoglycans contribute to the structural link between the neural retina and retinal pigment epithelium via the interaction with hyaluronan, which is also abundant in the IPM. Furthermore, several chondroitin sulfate proteoglycans in the nerve fiber-rich layers contain the hyaluronan-binding domain, so it is likely that the interaction of proteoglycans with hyaluronan plays an important role in neural network formation in the central nervous system.