Angiopoietin-1 Knockout Mice as a Genetic Model of Open-Angle Glaucoma
Benjamin R. Thomson, Marta Grannonico, Feng Liu, Mingna Liu, Parrykumar Mendapara, Ying Xu, Xiaorong Liu, Susan E. Quaggin
Abstract
Purpose: conditional knockout mice may provide one such model. Angiopoietin/TEK (ANGPT/TEK) signaling is crucial for SC formation and integrity in mice and humans, and mice lacking TEK or its ligand ANGPT1 develop a hypomorphic SC insufficient for normal aqueous humor outflow. Methods: inducible knockout mice, especially focusing on retina morphology and function. Results: deletion resulted in persistent ocular hypertension beginning in the first month after birth and leading to decreased visual acuity with age due to glaucomatous neuropathy. In the neural retina, we identified marked and specific loss of the retinal ganglion cells, whereas other retinal neurons exhibited largely normal morphology and patterning. Electroretinogram recordings demonstrated reduced scotopic threshold response, further indicating loss of retinal ganglion cell function. Conclusions: conditional knockout mice as a valuable new glaucoma model. Translational Relevance: knockout mice will provide an additional tool for studies of IOP-induced neural damage, mechanisms of disease progression, and novel treatment strategies.