Age-Related Spontaneous Corneal Lesions That Are Found Predominantly in Female CD36KO Mice

Abstract

Purpose:: The CD36 receptor functions as a multi-ligand scavenger receptor that is expressed on macrophages, dendritic cells, and corneal epithelial cells. CD36 receptors in the cornea are known to: (i) bind thrombospondin (TSP-1), (ii) inhibit angiogenesis and (iii) facilitate corneal wound healing and prevent inflammation. One of its main functions on macrophages is to clear apoptotic cells. In the absence of CD36, the failure to clear DNA could induce autoimmunity through the development of anti-nuclear antibodies. We hypothesize that in the absence of CD36 receptors in the cornea, mice develop spontaneous corneal lesions with age as a consequence of delayed corneal wound healing, increased inflammation, and the development of autoimmunity.

Methods:: CD36KO mice, TSP-1KO mice, and wild-type C57BL/6 mice were screened via slit lamp examination for spontaneous corneal lesions as the mice aged (up to 16 months old). Corneas containing lesions were recovered, sectioned, stained, and examined microscopically. Serum was collected and analyzed for the presence of ANA (anti-nuclear antibodies).

Results:: Neither wild-type, nor TSP-1KO mice (up to 14 months old) displayed spontaneous corneal lesions at any age. By contrast, CD36KO mice displayed spontaneous corneal lesions that increased in frequency and severity with age. At 2 months only 10% of the mice displayed mild corneal lesions consisting of a central corneal opacification. At 16 months all mice displayed either mild, or severe lesions which consisted of a large dense opaque lesion protruding from the cornea. Histologically, severe lesions revealed a massive central infiltrate (which was CD45 positive) with few epithelial cells, but a relatively normal posterior stroma and endothelium. Surprisingly, the frequency of corneal lesions in the entire colony (irrespective of age) revealed that 74% of female mice displayed corneal lesions, as compared with only 26% of male mice. Anti-nuclear antibodies were found in the serum of older female mice, but not in the serum of wild-type mice.

Conclusions:: CD36KO mice develop spontaneous central corneal lesions that are more prevalent in female mice and increase in severity with age. The appearance of these lesions coincides with reduced corneal wound healing, reduced clearance of apoptotic cells, and the appearance of autoimmunity.

Keywords: cornea: epithelium • inflammation • autoimmune disease