Keratocyte depletion by genetic manipulation recreates corneal ectasia in a mouse model

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 (I-KeramTmG/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. We found that genetic ablation of keratocytes in first 20 days of life induce corneal thinning and ectasia. Corneal hydrops like phenotype -severe ectasia- occurred more frequently if keratocyte death was induced in first week of life. Inducing keratocyte death at an age where some degree of corneal maturation has occurred, over 3 weeks of life, did not create changes in corneal thickness, transparency, curvature or any noticeable abnormalities in microstructure.