Temporal Deletion of AP-2β in Postnatal Mice Demonstrates Distinct Roles in Anterior Angle Development and Intraocular Pressure Homeostasis

Purpose: The purpose of this study was to investigate how the loss of activating protein 2β (AP-2β) in either the early postnatal or adult mouse eye affects the trabecular meshwork (TM) and intraocular pressure (IOP) homeostasis. Methods: UbCreERT2+/-; Tfap2b-/lox; tdTomatolox/+ (UbCre/AP-2β-KO or mutant) and UbCreERT2+/-; Tfap2b+/lox; tdTomatolox/+ (control) pups were exposed to tamoxifen via intraperitoneal injection once daily from postnatal day 4 (P4) to P7 and were euthanized at P14. To investigate adult tissue, tamoxifen exposure occurred from P22 to P25. IOP measurements were taken at P40, P60, or P90 followed by euthanasia. Hematoxylin and eosin (H&E), immunohistochemistry (IHC) and transmission electron microscopy (TEM) were performed to assess the TM, retinal ganglion cells (RGCs), and retinal inflammation. Results: Loss of AP-2β in early postnatal (P4 to P7) mice showed a partially closed iridocorneal angle and absence of the TM and Schlemm's canal (SC); however, loss of AP-2β in adult mice (P22-P25) produced an open-angle phenotype with preserved outflow pathway structures. Despite maintaining an open-angle phenotype, these mutant mice demonstrated elevated IOP. Ultrastructural analysis revealed flattened vacuoles surrounding the SC, along with pigment dispersion and disrupted extracellular matrix architecture. Additionally, increased IOP was associated with a significant RGC loss, reduced retinal thickness, and increased retinal inflammation. Conclusions: Early postnatal loss of AP-2β resulted in impaired development of aqueous outflow structures. Loss of AP-2β in adult mice showed an open-angle phenotype, elevated IOP, and marked retinal abnormalities. Together, these outcomes reveal a dual requirement for AP-2β in anterior angle development and TM and IOP homeostasis.