Maldevelopment of Schlemm's Canal in Children with Glaucoma

To understand the role of vascular signaling networks in Schlemm’s canal development.

The Schlemm’s canal and the trabecular meshwork are aqueous humor outflow tissues in the eye that are critical for the regulation of intraocular pressure – a key determinant of glaucoma. Development of the Schlemm’s canal is affected in several early-onset glaucomas. This application will elucidate the role of Apelin receptor in Schlemm’s canal development and pediatric glaucomas types.

Apelin signaling in SC development has not been studied to date. The proposed work incorporates the latest, most powerful tools, including i) a conditional and inducible mouse line to spatially and temporally delete Aplnr during key stages of SC development, ii) single cell transcriptomics to determine the mechanism of Aplnr action on SC development, and iii) modern imaging technologies including high-resolution spectral-domain optical coherence tomography (SD-OCT) and confocal imaging with 3-D image rendering using Imaris.

Understand the role of Apelin signaling is crucial for the treatment of congenital glaucoma where SC development is impaired. Pediatric patients with glaucoma typically have a poor vision prognosis. Lowering of IOP remains the only approved method to preserve visual function in these patients and surgery often fails over time due to the formation of scar tissue, necessitating a re-imagined treatment paradigm. Aplnr can potentially serve as a target to promote SC development. Mechanistic outcomes from this proposal will create avenues to design and test small molecule and genetic therapies targeting the Apelin pathway as a new-age treatment for pediatric glaucomas.