Usher syndrome type 1B is a combined deaf-blindness condition caused by mutations in the
gene. The loss of function of Myo7A protein in the RPE and photoreceptors leads
to blindness. We have evaluated the impact of subretinally delivered UshStat
, a recombinant
minimal equine infectious anaemia virus- (EIAV) based vector expressing human
photoreceptor function in response to different light intensities in
mice, a mouse model
of Usher type 1 B. Subretinal injections of EIAV CMV GFP or EIAV CMV MYO7A (UshStat
were performed in
mice. Photoreceptor function in EIAV CMV MYO7A treated eyes
was determined histologically by evaluating alpha-transducin translocation in photoreceptors
in response to low and high light levels. In addition, the neuroprotection from photoreceptor
degeneration in response to chronic light intensity was evaluated. Subretinal delivery of EIAV
vectors in the mouse lead to gene transfer and expression in photoreceptors and RPE cells.
mouse model lacking functional Myo7A, subretinal delivery of the UshStat
protected photoreceptors from intense light damage as indicated by reduced photoreceptor
cell loss and restored threshold for translocation of alpha-transducin in the photoreceptors.
tolerability in the macaque following the subretinal injection is ongoing. We have
shown that subretinal delivery of UshStat
is able to restore the alpha-transducin translocation
phenotype in the
mouse model and neuroprotect the photoreceptors from high light
intensity damage. These data support the development of an EIAV-based gene replacement
therapy to treat Usher type 1B syndrome.
Dominic Cosgrove received his Ph.D. in Biochemistry from University of Nebraska Medical Center in 1989 and did his post-doc at the Faculte de Medicine (CNRS) in Strasbourg France. He has been the director of the gene expression laboratory at BTNRH since 1991. His research interests focus on defining the molecular mechanisms of Usher syndrome and Alport syndrome.
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