Spontaneous development of corneal crystalline deposits in MRL/Mp mice.
OBJECTIVE
The presence of corneal opacities associated with dacryoadenitis and lacrimal gland destruction has led investigators to consider MRL/Mp mice as models for band keratopathy and Sjögren syndrome. In this study, the authors examined the time course of the corneal opacification and investigated whether the opacities were associated with altered serum levels of parathyroid hormone, calcium, and phosphorus, as well as quantitative and qualitative differences in tear production.


METHODS
Corneas were analyzed microscopically and tear fluid production was measured by a modified Schirmer test.


RESULTS
Corneal lesions were observed as early as the fifth week after birth. The lesions consisted of calcium phosphate and appeared as punctate, crystalline opacities located subeithelially. Lesions were present in 72% (56 of 78) of the MRL/Mp mice, with no significant difference in incidence between MRL/Mp +/+ and MRL/Mp lpr/lpr mice. Corneal calcification was occasionally associated with a self-limiting keratitis and neovascularization. In control mice, corneal opacities were not observed before the animals were 6 months of age. Levels of circulating parathyroid hormone decreased significantly during the first 16 weeks of age in MRL/Mp mice. In addition, MRL/Mp mice of both sexes had a significantly lower tear fluid production as compared to BALB/c mice of the same age.


CONCLUSIONS
Because corneal lesions start to develop in 5-week-old MRL/Mp mice, thereby preceding the clinical signs of systemic autoimmune disease, and may develop in 6-month-old nonautoimmune-prone mice, it is suggested that calcification develops independent of the systemic autoimmune disease and might be restricted to the cornea.
Verhagen
C
C
Department of Opthalmology, University of Amsterdam, The Netherlands.
Rowshani
T
T
Willekens
B
B
van Haeringen
N J
NJ
D000818:Animals; D001327:Autoimmune Diseases / Q000097:blood / Q000473:pathology*; D002114:Calcinosis / Q000097:blood / Q000473:pathology*; D002118:Calcium / Q000097:blood; D003315:Cornea / Q000473:pathology; D003316:Corneal Diseases / Q000097:blood / Q000473:pathology*; D003318:Corneal Opacity / Q000097:blood / Q000473:pathology; D004577:Electron Probe Microanalysis; D005260:Female; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D013666:Tears / Q000378:metabolism
D010281:Parathyroid Hormone; D010758:Phosphorus; D002118:Calcium