Plasticity of ocular surface epithelia: Using a murine model of limbal stem cell deficiency to delineate metaplasia and transdifferentiation

Maintaining corneal health and transparency are necessary pre-requisites for exquisite vision, a function ascribed to stem cells (SCs) nestled within the limbus. Perturbations to this site or depletion of its SCs results in limbal SC deficiency. While characterizing a murine model of this disease, we discovered unusual transformation phenomena on the corneal surface including goblet cell metaplasia (GCM), conjunctival transdifferentiation, and squamous metaplasia (SQM). GCM arose from K8(+) differentiated conjunctival epithelial cells when the limbus was breached and was exacerbated by neovascularization. Regions within the cornea that harbored newly transformed K12(+) epithelia were void of blood vessels and GCs, suggesting that the cornea also initiated a self-repair program. Knowledge of the intrinsic circuits that contribute to cell identity change in lineage-restricted epithelia will be invaluable for designing new therapeutics for patients with blinding corneal disease.