Toward an understanding of Norrie disease and the putative growth factor norrin

Norrie disease is an X-linked recessive syndrome characterized by congenital blindness and often accompanied by deafness and mental retardation.;Analysis of Ndp gene expression has demonstrated a pattern of expression in the eye, brain, and inner ear that begins late in development and is maintained throughout adulthood. In the eye, expression begins in the ganglion cell layer and spreads into the outer cell layers. In the ear, expression begins slightly later and is seen in the marginal cells of the stria vascularis and spiral ganglion cells indicating a potential regulatory role in the maintenance of these cell types.;The protein structure and binding characteristics of norrin suggest that it is a secreted growth factor or growth factor antagonist with limited capacity to diffuse. Therefore, norrin may influence the cells in which it is expressed or those in very close proximity. Although a specific target for norrin binding has not been identified, its ability to bind to the tissues from which it is expressed, with particular binding to areas of high neural fiber density, suggest the presence of at least one specific target for norrin interaction.;Analysis of the knockout mouse model hearing phenotype has demonstrated an age-related hearing loss similar to that found in human Norrie disease. In the ear, histological analysis demonstrates significant loss of spiral ganglion neurons as well as all cell types in the stria vascularis. In addition, sporadic loss of the organ of Corti is notable. These observations suggest that norrin plays a primary role in the spiral ganglion and stria, vascularis.;The discovery of a Costa Rican family with Norrie disease, combined with a cosegregating vascular phenotype, provides evidence for the importance of the vascular system as a potential target for norrin actions. In addition, analysis of the optic and cochlear vasculatures in the knockout mouse model has revealed defects in these structures, further supporting a role for norrin in the vasculature. While the underlying causes of these defects have not been elucidated, some evidence suggests a defect in the cell types that closely interact with the vessels in the retina and cochlea.