Differential Accumulation of Glycosaminoglycans in the Retinas from a Mouse Model of Mucopolysaccharidosis I
Ophthalmic complications, including corneal clouding, retinopathy, and glaucoma, are common in patients with Mucopolysaccharidosis Type I (MPS I). Although previous research has shown that glycosaminoglycans (GAGs) accumulate in retinal tissue disrupting retinal function in patients with MPS I, the development timetable for retinal pathophysiology remains unclear. The purpose of this project was to visualize and measure GAG accumulation in a mouse model for MPS I. Using mice with a gene deletion for the enzyme alpha-L-iduronidase (IDUA), retinal tissues were sectioned and stained for GAGs using two methods. Tissue sections through the retina at the level of the optic nerve head in MPS I mice and litter-mate control mice were stained with Alcian blue stain, which allows the visualization of GAG accumulation. A computer morphometry program (Bioquant) was used to measure the density of the blue stain in various layers of the retina. For statistical analyses, slides were separated by the material the tissue was embedded in before sectioning- tragacanth gum and OCT. For the tissues embedded in tragacanth gum, mice with the IDUA knockout had a significantly greater density of blue stain than wildtype and heterozygous mice, indicating that the MPS I mice had greater GAG accumulation. However, this pattern was not demonstrated in the tissues embedded in OCT, where globally the density of GAG staining of the retinas was consistently less intense. Patterns of GAG accumulation in retinal tissue of MPS I mice will be confirmed with glycosaminoglycan-specific antibodies, perlecan and chondroitin sulfate. Initial examination demonstrated increased perlecan staining in both the IDUA knockout mice and the mice haploinsufficient for the IDUA gene. The goal of this continuing study will be to determine how and where GAG accumulation has the most significant impact on retinal function in order to increase understanding of the timetable for development of decreased retinal normalcy. Ultimately, the goal will be to assess the efficacy of existing treatments using knowledge gained by this study in order to improve visual outcomes.