Verhagen C, Rowshani T, Willekens B, van Haeringen N J
Department of Opthalmology, University of Amsterdam, The Netherlands.
Invest Ophthalmol Vis Sci. 1995 Feb;36(2):454-61.
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.
Corneas were analyzed microscopically and tear fluid production was measured by a modified Schirmer test.
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.
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.
角膜混浊与泪腺炎及泪腺破坏相关，这使得研究人员将MRL/Mp小鼠视为带状角膜病变和干燥综合征的模型。在本研究中，作者检查了角膜混浊的时间进程，并调查了混浊是否与甲状旁腺激素、钙和磷的血清水平改变以及泪液分泌的定量和定性差异有关。
对角膜进行显微镜分析，并通过改良的泪液分泌试验测量泪液分泌。
早在出生后第五周就观察到角膜病变。病变由磷酸钙组成，表现为位于上皮下的点状、结晶状混浊。72%（78只中的56只）的MRL/Mp小鼠出现病变，MRL/Mp +/+和MRL/Mp lpr/lpr小鼠的发病率无显著差异。角膜钙化偶尔与自限性角膜炎和新生血管形成有关。在对照小鼠中，在动物6个月大之前未观察到角膜混浊。MRL/Mp小鼠在16周龄前循环甲状旁腺激素水平显著下降。此外，与相同年龄的BALB/c小鼠相比，两性的MRL/Mp小鼠泪液分泌明显减少。
由于角膜病变在5周龄的MRL/Mp小鼠中开始发展，早于系统性自身免疫疾病的临床症状，并且可能在6个月大的非自身免疫易感小鼠中发展，因此提示钙化的发生独立于系统性自身免疫疾病，并且可能局限于角膜。
