Notch signaling in the pigmented epithelium of the anterior eye segment promotes ciliary body development at the expense of iris formation

The ciliary bodyand iris are pigmented epithelial structures in the anterior eye segment that function to maintain correct intra-ocular pressure and regulate exposure of the internal eye structures to light, respectively. The cellular and molecular factors that mediate the development of the ciliary bodyand iris from the ocular pigmented epithelium remain to be fully elucidated. Here, we have investigated the role of Notchsignaling during the development of the anterior pigmented epithelium by using genetic loss- and gain-of-function approaches. Loss of canonical Notchsignaling results in normal iris development but absence of the ciliary body. This causes progressive hypotony and over time leads to phthisis bulbi, a condition characterized by shrinkage of the eye and loss of structure/function. Conversely, Notchgain-of-function results in aniridiaand profound ciliary bodyhyperplasia, which causes ocular hypertensionand glaucoma-like disease. Collectively, these data indicate that Notchsignaling promotes ciliary bodydevelopment at the expense of iris formation and reveals novel animal models of human ocular pathologies.