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Corneal endothelium in mucopolysaccharide storage disorders. Morphologic studies in animal models
R J Mollard1, P Telegan, M Haskins
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
Abstract:
In the systemic mucopolysaccharidoses (MPS) in animals, corneal clouding resulted from storage of glycosaminoglycans (GAG) in stromal keratocytes. The corneal epithelium was normal (MPS VI and VII) or minimally affected (MPS I), and stromal edema was not a feature even though the corneal endothelium demonstrated variable pathology. The MPS I (cat) cornea showed endothelial cells with large numbers of secondary lysosomal inclusions that were vacuolated or had a granular matrix. The endothelium was uniformly affected, but was not markedly hypertrophied. In contrast, the MPS VI (cat) cornea showed no endothelial cell disease. The MPS VII (dog) cornea had the most significant and dramatic endothelial pathology. The cells were massively hypertrophied and contained large numbers of vacuolated lysosomal inclusions. Regardless of the severity of the morphologic disease, the endothelial cells in these animal models functioned normally in maintaining the relative dehydration of the cornea. The corneal clouding was the result of storage in stromal keratocytes rather than corneal edema from endothelial dysfunction.
Insights
Corneal clouding in animal models of mucopolysaccharidoses (MPS) stems from GAG storage in stromal keratocytes, not endothelial dysfunction. This finding clarifies the cause of vision impairment in these genetic storage diseases.
Area of Science:
- Ophthalmology
- Genetics
- Veterinary Medicine
Background:
- Systemic mucopolysaccharidoses (MPS) are genetic disorders characterized by glycosaminoglycan (GAG) accumulation.
- Corneal clouding is a common clinical sign in various MPS types, impacting vision.
- Previous understanding of MPS corneal pathology focused on endothelial involvement.
Purpose of the Study:
- To investigate the cellular basis of corneal clouding in animal models of MPS.
- To differentiate the roles of corneal epithelium, stroma, and endothelium in MPS-related corneal opacity.
- To determine if endothelial dysfunction contributes to corneal edema in MPS.
Main Methods:
- Histopathological examination of corneas from animal models of MPS I (cat), MPS VI (cat), and MPS VII (dog).
- Assessment of GAG storage in corneal stromal keratocytes and endothelial cells.
- Evaluation of corneal epithelial and endothelial morphology and function.
Main Results:
- Corneal clouding was consistently associated with GAG storage within stromal keratocytes across all MPS models.
- Corneal epithelium was normal or minimally affected; stromal edema was absent.
- Endothelial pathology varied, with MPS VII dogs showing significant cellular hypertrophy and inclusions, yet endothelial function remained normal.
- MPS I cats had endothelial inclusions, while MPS VI cats showed no endothelial disease.
Conclusions:
- Corneal clouding in these animal MPS models is primarily caused by GAG accumulation in stromal keratocytes.
- Endothelial dysfunction is not the primary driver of corneal opacity or edema in these MPS models.
- The findings highlight stromal keratocyte storage as the key factor in MPS-induced corneal clouding, irrespective of endothelial changes.