RT Journal Article
SR Electronic
T1 Intravitreal Gene Therapy Reduces Lysosomal Storage in Specific Areas of the CNS in Mucopolysaccharidosis VII Mice
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3302
OP 3307
DO 10.1523/JNEUROSCI.23-08-03302.2003
VO 23
IS 8
A1 Anne K. Hennig
A1 Beth Levy
A1 Judith  Mosinger Ogilvie
A1 Carole A. Vogler
A1 Nancy Galvin
A1 Steven Bassnett
A1 Mark S. Sands
YR 2003
UL http://www.jneurosci.org/content/23/8/3302.abstract
AB The mucopolysaccharidoses (MPSs) are lysosomal storage diseases resulting from impaired catabolism of sulfated glycosaminoglycans. MPS VII mice lack lysosomal β-glucuronidase (GUSB) activity, leading to the accumulation of partially degraded chondroitin, dermatan, and heparan sulfates in most tissues. Consequently, these mice develop most of the symptoms exhibited by human MPS VII patients, including progressive visual and cognitive deficits. To investigate the effects of reducing lysosomal storage in nervous tissues, we injected recombinant adeno-associated virus encoding GUSB directly into the vitreous humor of young adult mice. Interestingly, GUSB activity was subsequently detected in the brains of the recipients. At 8–12 weeks after treatment, increased GUSB activity and reduced lysosomal distension were found in regions of the thalamus and tectum that received inputs from the injected eye. Lysosomal storage was also reduced in adjacent nonvisual regions, including the hippocampus, as well as in the visual cortex. The findings suggest that both diffusion and trans-synaptic transfer contribute to the dissemination of enzyme activity within the CNS. Intravitreal injection may thus provide a means of delivering certain therapeutic gene products to specific areas within the CNS.