In man, mutations of the
megalin-encoding gene causes the rare Donnai-Barrow/
Facio-Oculo-Acoustico-Renal Syndrome, which is partially characterized by high-grade
myopia. Previous studies of renal
megalin function have established that
megalin is crucial for conservation of renal filtered nutrients including
vitamin A; however, the role of
megalin in ocular physiology and development is presently unknown. Therefore, we investigate ocular
megalin expression and the ocular phenotype of
megalin-deficient mice. Topographical and subcellular localization of
megalin as well as the ocular phenotype of
megalin-deficient mice were examined with immunological techniques using light, confocal and electron microscopy. We identified
megalin in the retinal pigment epithelium (RPE) and non-pigmented ciliary body epithelium (NPCBE) in normal mouse eyes. Immunocytochemical investigations furthermore showed that
megalin localizes to vesicular structures in the RPE and NPCBE cells. Histological investigations of ocular mouse tissue also identified a severe
myopia phenotype as well as enlarged RPE melanosomes and abnormal ciliary body development in the
megalin-deficient mice. In conclusion, the complex ocular phenotype observed in the
megalin-deficient mice suggests that
megalin-mediated developmental abnormalities may contribute to the high
myopia phenotype observed in the
Donnai-Barrow Syndrome patients and, thus, that
megalin harbors important roles in ocular development and physiology. Finally, our data show that
megalin-deficient mice may provide a valuable model for future studies of
megalin in ocular physiology and pathology.