A Story of Three Blind Mice: Characterization of Retinopathy of Hurler's Disease

Abstract

Mucopolysaccharidosis is a class of lysosomal storage disorders where a genetic mutation results in a deficiency of enzymes that would normally break down glycosaminoglycans (GAGs) in cells. This disorder results in the accumulation of GAGs in all virtually all cells leading to tissue and organ damage. Mucopolysaccharidosis I-H or Hurler’s disease, a fatal genetic condition, is the most extreme form due to a deficiency of the enzyme α-L-iduronidase. Although life-expectancy is increased with treatment, vision loss are still present in a number of patients. A better understanding of the abnormalities in the retina is essential in choosing a treatment to prevent vision loss. A mouse model of MPS I, or Hurler mouse, was studied for visual function, specific abnormalities in the retina, and success of two different modalities of treatment in the prevention of vision loss. First, the Hurler mice showed large variations in retinal morphology – from normal in appearance to extremely abnormal. Abnormalities ranged from severe, in which the optic nerve fails to exit the eye and ganglion cell loss, to milder irregularities such as GAGs deposits and disorganization of the retinal layers. An optomotor test, the ability to track black and white stripes on a rotating drum, was used to assess overall visual function. Approximately 25% of Hurler mice were unilaterally blind. Visual function was preserved in the intranasal treatment group, while Hurler mice subjected to a hematopoietic stem cell transplantation treatment experienced vision loss. These results suggest that an intranasal treatment may have protective effects on vision in the treatment of Mucopolysaccharidosis I-H or Hurler’s disease.