Keratocyte Depletion by Genetic Manipulation Re-creates Corneal Ectasia in a Mouse Model.

Abstract

Corneal ectasias are a significant cause of vision morbidity worldwide. In humans, corneal ectasias are characterized by tissue mechanical weakening, stromal thinning, and bulging. Previous histopathology studies showed a high rate of keratocyte apoptosis in corneas with ectasia. A mouse model expressing a keratocyte lineage-specific reporter KeraRT/tetO-Cre/mTmG/DTR was created to elucidate the roles of keratocyte death in the development of corneal ectasias. This mouse model allows selective death of keratocytes at chosen times during stromal development and in mature stromas. Slit-lamp examination as well as histopathology and advanced imaging techniques were used to assess stromal structure after keratocyte genetic ablation. It was found that genetic ablation of keratocytes in the first 20 days after birth induces corneal thinning and ectasia. A corneal hydrops-like phenotype (severe ectasia) occurred more frequently if keratocyte death was induced in the first week after birth. Inducing keratocyte death at an age where some degree of corneal maturation has occurred, >3 weeks of age, did not create changes in corneal thickness, transparency, or curvature, or any noticeable abnormalities in microstructure.