Retinal function is improved in a murine model of a lysosomal storage disease following bone marrow transplantation

Mucopolysaccharidoses are heritable lysosomal storage diseases caused by de ficiencies in acid hydrolases involved in the sequential degradation of com plex glycosaminoglycans (GAGs). In many mucopolysaccharidoses, GAGs accumul ate in the retinal pigment epithelial (RPE) cells of the eye resulting in p ronounced lysosomal distension. Tt is not clear how the progressive accumul ation of GAGs affects retinal function. Bone marrow transplantation (BMT) i s a relatively effective therapy for many lysosomal storage diseases and ca n result in a dramatic reduction in lysosomal distention in the RPE. Althou gh effective at reducing lysosomal storage, it is not clear how effective s yngeneic BMT is at treating retinal dysfunction. Here we show that there is a progressive decrease in the amplitudes of both the dark-adapted (rod-con e) and light-adapted (cone-dominated) flash electroretinograms (ERG) betwee n 8 and 20 weeks of age in a murine model of mucopolysaccharidosis type VII (MPS VII). By 20 weeks, the average dark-adapted b-wave amplitude was 118 muV in MPS VII mice as compared to 469 muV in normal mice of the same strai n. MPS VII mice receiving syngeneic BMT at 4 weeks of age have reduced lyso somal storage in retinal pigment epithelial cells and normal ERG amplitudes at 20 weeks of age. Retinal function is impaired in untreated 8 week old M PS VII mice. Following BMT at 8 weeks, rod-cone-and cone-dominated response s recovered to within the normal range by 20 weeks of age. These data demon strate the temporal pattern of retinal dysfunction in the MPS VII mouse and indicate that BMT can reduce the lysosomal storage and improve retinal fun ction. (C) 2000 Academic Press.