| First Author | Taiyab A | Year | 2022 |
| Journal | J Neurosci Res | Volume | 100 |
| Issue | 2 | Pages | 638-652 |
| PubMed ID | 34822722 | Mgi Jnum | J:319392 |
| Mgi Id | MGI:6863841 | Doi | 10.1002/jnr.24982 |
| Citation | Taiyab A, et al. (2022) Deletion of transcription factor AP-2beta from the developing murine trabecular meshwork region leads to progressive glaucomatous changes. J Neurosci Res 100(2):638-652 |
| abstractText | Glaucoma is one of the leading causes of irreversible blindness and can result from abnormalities in anterior segment structures required for aqueous humor outflow, including the trabecular meshwork (TM) and Schlemm's canal (SC). Transcription factors such as AP-2beta play critical roles in anterior segment development. Here, we show that the Mgp-Cre knock-in (Mgp-Cre.KI) mouse can be used to target the embryonic periocular mesenchyme giving rise to the TM and SC. Fate mapping of male and female mice indicates that AP-2beta loss causes a decrease in iridocorneal angle cells derived from Mgp-Cre.KI-expressing populations compared to controls. Moreover, histological analyses revealed peripheral iridocorneal adhesions in AP-2beta mutants that were accompanied by a decrease in expression of TM and SC markers, as observed using immunohistochemistry. In addition, rebound tonometry showed significantly higher intraocular pressure (IOP) that was correlated with a progressive significant loss of retinal ganglion cells, reduced retinal thickness, and reduced retinal function, as measured using an electroretinogram, in AP-2beta mutants compared with controls, reflecting pathology described in late-stage glaucoma patients. Importantly, elevated IOP in AP-2beta mutants was significantly reduced by treatment with latanoprost, a prostaglandin analog that increases unconventional outflow. These findings demonstrate that AP-2beta is critical for TM and SC development, and that these mutant mice can serve as a model for understanding and treating progressive human primary angle-closure glaucoma. |
