title: Ocular lesions in canine mucopolysaccharidosis I and response to enzyme replacement therapy.
abstract: OBJECTIVE
  Mucopolysaccharidosis I (MPS I) is an inherited metabolic disorder resulting from deficiency of α-L-iduronidase and lysosomal accumulation of glycosaminoglycans (GAG) in multiple tissues. Accumulation of GAG in corneal stromal cells causes corneal opacity and reduced vision. The purpose of this study was to determine the extent of ocular GAG accumulation and investigate the effectiveness of intravenous enzyme replacement therapy (ERT) on corneal GAG accumulation in dogs.
  
  
  METHODS
  Ocular tissues were obtained from 58 dogs with mucopolysaccharidosis I and four unaffected controls. Affected dogs received either low-dose ERT, high-dose ERT, or no treatment; some low-dose dogs also received intrathecal treatments. Histologic severity of corneal stromal GAG accumulation was scored.
  
  
  RESULTS
  Accumulation of GAG was found in corneal stromal cells and scleral fibroblasts but not in corneal epithelium, endothelium, ciliary epithelium, choroid, retina, retinal pigment epithelium, or optic nerve. Corneal GAG accumulation increased in severity with increasing age. Although low-dose ERT did not significantly reduce corneal stromal GAG accumulation in comparison with untreated animals, high-dose ERT did result in significantly less GAG accumulation compared with the untreated dogs (adjusted P = 0.0143) or the low-dose ERT group (adjusted P = 0.0031). Intrathecal treatments did not significantly affect GAG accumulation. Dogs that began ERT shortly after birth also had significantly less (P < 0.0001) GAG accumulation in the corneal stroma than dogs with a later onset of treatment.
  
  
  CONCLUSIONS
  These data suggest that high-dose, intravenous ERT is effective at preventing and/or clearing corneal stromal GAG accumulation, particularly if initiated early after birth.
authors: Department of Pathobiology, University of Tennessee, College of Veterinary Medicine, Knoxville, Tennessee 37996, USA. knewkirk@utk.edu
authors: Kim M
authors: KM
authors: Newkirk
authors: Rosalie M
authors: RM
authors: Atkins
authors: Patti I
authors: PI
authors: Dickson
authors: Barton W
authors: BW
authors: Rohrbach
authors: Michael F
authors: MF
authors: McEntee
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D003316:Corneal Diseases / Q000188:drug therapy / Q000201:enzymology / Q000662:veterinary*; D003319:Corneal Stroma / Q000378:metabolism; D004283:Dog Diseases / Q000188:drug therapy* / Q000201:enzymology; D004285:Dogs; D056947:Enzyme Replacement Therapy / Q000662:veterinary*; D005347:Fibroblasts / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism / Q000648:ultrastructure; D007068:Iduronidase / Q000008:administration & dosage / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008059:Mucopolysaccharidosis I / Q000188:drug therapy / Q000201:enzymology / Q000662:veterinary*; D012189:Retrospective Studies; D012590:Sclera / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; D007068:Iduronidase