title: A novel explanation of corneal clouding in a bone marrow transplant-treated patient with Hurler syndrome.
abstract: One common complication of mucopolysaccharidosis I-Hurler (MPS1-H) is corneal clouding, which occurs despite current treatments, including bone marrow transplantation. Human corneas were obtained from a 14 year old subject with MPS1-H and visual disability from progressive corneal clouding despite a prior bone marrow transplant at age 2. This was compared to a cornea from a 17 year old donated to our eye bank after his accidental death. The corneas were analyzed microscopically after staining with Alcian blue, antibodies to collagen I, IV, VI, and α-smooth muscle actin. Differences in levels of expression of the indicated molecules were assessed. Corneas from Hurler and control mice were examined similarly to determine potential mechanistic overlap. The MPS1-H subject cornea showed elevations in mucopolysaccharide deposition. The MPS1-H and Hurler mice corneas showed increased and disorganized expression of collagen I and IV relative to the control corneas. The MPS1-H corneas also showed increased and disordered expression of collagen VI. Positive expression of α-smooth muscle actin indicated myofibroblast conversion within the MPS1-H cornea in both the patient and mutant mouse material compared to normal human and control mouse cornea. Increased deposition of collagens and smooth muscle actin correlate with corneal clouding, providing a potential mechanism for corneal clouding despite bone marrow transplantation in MPS1-H patients. It might be possible to prevent or slow the onset of corneal clouding by treating the cornea with drugs known to prevent myofibroblast conversion.
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Ching
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA; Department of Pediatrics, University of Minnesota, USA.
authors.forename: Erick D
authors.initials: ED
authors.lastname: Bothun
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA; Minnesota Eye Consultants, PA, Minnetonka, MN, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Hardten
authors.affiliation: Stem Cell Institute, University of Minnesota, USA; Department of Pediatrics, University of Minnesota, USA.
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.affiliation: Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA; Stem Cell Institute, University of Minnesota, USA; Department of Neuroscience, University of Minnesota, Minneapolis, MN, USA. Electronic address: mcloo001@umn.edu.
authors.forename: Linda K
authors.initials: LK
authors.lastname: McLoon
mesh_terms: D000293:Adolescent; D000818:Animals; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D003094:Collagen / Q000378:metabolism*; D003318:Corneal Opacity / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008059:Mucopolysaccharidosis I / Q000150:complications* / Q000628:therapy; D058628:Myofibroblasts / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; D003094:Collagen
keywords: Collagen; Cornea; Corneal clouding; Hurler syndrome; Mucopolysaccharidosis I; Myofibroblasts