Differential Accumulation of Glycosaminoglycans in the Retinas of a Mouse Model for Mucopolysaccharidosis Type I
Mucopolysaccharidosis Type I (MPS I) is a genetic disorder characterized by a deficiency in the enzyme 𝛼-L-iduronidase (IDUA), leading to the accumulation of glycosaminoglycans (GAGs) in various tissues throughout the body causing a wide range of symptoms. GAGs accumulate in ocular tissues causing multiple ophthalmic complications, resulting in reduced vision. While it was previously established that GAG accumulation in the retina negatively affects visual outcomes, the pathophysiology of retinal GAG accumulation and its impact remained unclear. The purpose of this study was to visualize the localization and measure the levels of GAG accumulation in retinal tissues from a mouse model with MPS I. Mice with three genotypes were used; IDUA gene knockout mice and mice haploinsufficient for the gene modeled varying severities of MPS I and were compared to a wild-type control. Sections of retinal tissues were stained with Alcian blue and GAG-specific antibodies perlecan monoclonal antibody, heparan sulfate proteoglycan, and chondroitin sulfate proteoglycan. The density of the stains was measured with a computer-compatible morphometry program, revealing that MPS I tissues showed increased GAG accumulation compared to the wild-type control across every staining technique. Immunofluorescent staining provided insight into the localization of specific GAGs in the various layers of the retina. Insight into the pathophysiology of GAG accumulation in the retina will allow for the evaluation of its effects on visual outcomes and the efficacy of existing treatments for MPS I.