June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Role of Transcription Factor AP-2β in the Development of the Trabecular Meshwork and Schlemm’s Canal
Author Affiliations & Notes
  • Aftab Taiyab
    McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada
  • Monica Akula
    McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada
  • Japnit Dham
    Medical Sciences, McMaster University, Hamilton, Ontario, Canada
  • Mark Rzepka
    McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada
  • Terete Borras
    University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States
  • Trevor Williams
    University of Colorado - Anschutz Medical Campus, Aurora, Colorado, United States
  • Judith A West-Mays
    McMaster University Faculty of Health Sciences, Hamilton, Ontario, Canada
  • Footnotes
    Commercial Relationships   Aftab Taiyab, None; Monica Akula, None; Japnit Dham, None; Mark Rzepka, None; Terete Borras, None; Trevor Williams, None; Judith West-Mays, None
  • Footnotes
    Support  NIH EY025789
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1514. doi:
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      Aftab Taiyab, Monica Akula, Japnit Dham, Mark Rzepka, Terete Borras, Trevor Williams, Judith A West-Mays; Role of Transcription Factor AP-2β in the Development of the Trabecular Meshwork and Schlemm’s Canal. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1514.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Anterior segment dysgenesis stems from anomalies in anterior ocular structures, including the trabecular meshwork (TM), leading to abnormalities in aqueous humor production and outflow. In order to determine the specific contribution of transcription factor activating protein-2β (AP-2β) in the development of TM, we have recently developed a novel mouse model by deleting AP-2β specifically from the developing TM region (TMR) using a novel MgpCre mouse line, known to be expressed in periocular mesenchyme (POM), giving rise to the future TM.

Methods : MgpCre+/-; Tfap2b+/- mice were bred with Tfap2blox/lox; tdTomatolox/lox mice to generate MgpCre+/-; Tfap2b-/lox; tdTomatolox/+ mice (AP-2β TMR KO) with Tfap2b, encoding AP-2β, deleted from the TMR. When crossed with tdTomato mice, control (MgpCre+/-; tdTomatolox/+) and knockout (KO) mice (MgpCre+/-; Tfap2b-/lox; tdTomatolox/+) expressed an RFP variant that was used to trace MgpCre-expressing cells in frozen sections. H&E and immunohistochemistry (IHC) of paraffin sections was carried out using antibodies for the TM markers, αSMA and myocilin, the Schlemm’s canal marker, Prox1, and retinal ganglion cell (RGC) marker, Brn3a, while intraocular pressure (IOP) was acquired using a tonometer.

Results : In control, MgpCre was expressed at embryonic day (E) 15.5 in the POM that was observed to be similar in AP-2β TMR KO as well. By P7 and P14, fewer tdTomato-positive cells were observed in the TMR of KO mice when compared with control mice. Fewer TM cells were observed in the KOs, as seen using H&E staining, and by the reduction in αSMA and myocilin staining. Further, absence of Prox1 staining was observed in the anterior angle of KO when compared to the control mice. A significant increase in IOP at P30 (n=6 eyes, p<0.001) followed by a significant reduction in retinal thickness (n=3 eyes, p<0.01) and Brn3a positive cells (n=3 eyes, p<0.01) at P40 was observed in the KO mice when compared with control.

Conclusions : The reduction in tdTomato-positive cells and the reduced expression of TM and Schlemm’s canal markers in the AP-2β TMR KO mice suggests that AP-2β is critical for the development and differentiation of TMR. The increased IOP at P30 in the KO mice likely resulted from abnormal differentiation of the POM cells into TM cells. The decreased retinal thickness and Brn3a positive cells at P40 shows loss of RGCs that can be attributed to increased IOP.

This is a 2021 ARVO Annual Meeting abstract.

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