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Investigative Ophthalmology & Visual Science, Vol 36, 1144-1154, Copyright © 1995 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Lens-specific expression of a major histocompatibility complex class I molecule disrupts normal lens development and induces cataracts in transgenic mice

WD Martin, RM Egan, JL Stevens and JG Woodward
Department of Microbiology and Immunology, University of Kentucky Medical Center, Lexington, USA.

PURPOSE. Lens epithelial tissue does not normally express major histocompatibility complex (MHC) class I molecules. In addition, the mechanism of self-tolerance to intraocular antigens is unknown. To study the effect of class I expression in the lens, transgenic mice were produced that express an allo-MHC class I molecule under the alpha A-crystallin proximal promoter. METHODS. p alpha Dd was generated by fusion of the H-2Dd structural gene to the alpha A-crystallin proximal promoter. Transgenic mice were produced, and founder lines were identified by Southern blot hybridization. Eyes from transgenic mice were cryostat sectioned and stained for Dd expression or fixed in paraformaldehyde and stained for histologic analysis. Lens RNA was isolated by acid phenol extraction, and transgene expression was analyzed by nuclease protection. RESULTS. The transgenic mice demonstrated dose-dependent, nonimmunologic lens defects consistent within a given line. In the highest expressing lines, ocular defects, including microphthalmia and cataract formation, were observed. Many adult mice from these lines demonstrated lens capsule rupture and a Dd- specific inflammatory response. Inflammation did not occur in mice with intact lens capsules. CONCLUSIONS. Overexpression of H-2Dd in the lens had serious nonimmunologic consequences on lens development and cataract formation. In addition, the high copy number mice revealed at least a partial loss of immunologic tolerance on lens capsule rupture. The lack of an inflammatory response in transgenic mice with intact lens capsules suggests that the physical barrier of the lens capsule is one mechanism of maintaining immune privilege.




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Copyright © 1995 by the Association for Research in Vision and Ophthalmology