Purpose: Our lab has shown that conditionally disrupting the transcription factor activating protein 2β (Tfap2b) gene, responsible for the activating protein-2β (AP-2β) transcription factor, exclusively in cranial neural crest cells (AP-2β NCC KO), leads to anterior segment dysgenesis and a closed angle phenotype. The purpose of the current study is to determine if there is a progressive loss of retinal ganglion cells (RGCs) in the mutant over time and whether this loss was associated with macroglial activity changes and elevated intraocular pressure (IOP). Methods: Using the Cre-loxP system, we generated a conditional knockout of Tfap2b exclusively in cranial NCC (AP-2β NCC KO). Immunohistochemistry was performed using anti-Brn3a, anti-GFAP and anti-Vimentin antibodies. IOP was measured using a tonometer and the data was analyzed using GraphPad Prism software. Brn3a and DAPI positive cells were counted using Image-J and statistical analysis was performed with GraphPad Prism software. Results: Our findings revealed that while no statistical difference in Brn3a expression was observed between wild-type and mutant mice at postnatal day (P) 4 or P10, at P40 (p < .01) and P42 (p < .0001) Brn3a expression was significantly reduced in the mutant retina at the region of the ONH. There was also increased expression of glial fibrillary acidic protein (GFAP) by Müller cells in the AP-2β NCC KO mice at P35 and P40, indicating the presence of neuroinflammation. Moreover, increased IOP was observed starting at P35 and continuing at P40 and P42 (p < .0001 for all three ages examined).Conclusions: Together, these findings suggest that the retinal damage observed in the KO mouse becomes apparent by P40 after increased IOP was observed at P35 and progressed over time. The AP-2β NCC KO mouse may therefore be a novel experimental model for glaucoma.
Purpose: Our lab has shown that conditionally disrupting the transcription factor activating protein 2β (Tfap2b) gene, responsible for the activating protein-2β (AP-2β) transcription factor, exclusively in cranial neural crest cells (AP-2β NCC KO), leads to anterior segment dysgenesis and a closed angle phenotype. The purpose of the current study is to determine if there is a progressive loss of retinal ganglion cells (RGCs) in the mutant over time and whether this loss was associated with macroglial activity changes and elevated intraocular pressure (IOP). Methods: Using the Cre-loxP system, we generated a conditional knockout of Tfap2b exclusively in cranial NCC (AP-2β NCC KO). Immunohistochemistry was performed using anti-Brn3a, anti-GFAP and anti-Vimentin antibodies. IOP was measured using a tonometer and the data was analyzed using GraphPad Prism software. Brn3a and DAPI positive cells were counted using Image-J and statistical analysis was performed with GraphPad Prism software. Results: Our findings revealed that while no statistical difference in Brn3a expression was observed between wild-type and mutant mice at postnatal day (P) 4 or P10, at P40 (p < .01) and P42 (p < .0001) Brn3a expression was significantly reduced in the mutant retina at the region of the ONH. There was also increased expression of glial fibrillary acidic protein (GFAP) by Müller cells in the AP-2β NCC KO mice at P35 and P40, indicating the presence of neuroinflammation. Moreover, increased IOP was observed starting at P35 and continuing at P40 and P42 (p < .0001 for all three ages examined).Conclusions: Together, these findings suggest that the retinal damage observed in the KO mouse becomes apparent by P40 after increased IOP was observed at P35 and progressed over time. The AP-2β NCC KO mouse may therefore be a novel experimental model for glaucoma.
Authors: Mao Mao; Adam Hedberg-Buenz; Demelza Koehn; Simon W M John; Michael G Anderson Journal: Invest Ophthalmol Vis Sci Date: 2011-04-01 Impact factor: 4.799
Authors: Andreas Bringmann; Thomas Pannicke; Jens Grosche; Mike Francke; Peter Wiedemann; Serguei N Skatchkov; Neville N Osborne; Andreas Reichenbach Journal: Prog Retin Eye Res Date: 2006-07-12 Impact factor: 21.198
Authors: Vanessa B Martino; Thomas Sabljic; Paula Deschamps; Rebecca M Green; Monica Akula; Erica Peacock; Alexander Ball; Trevor Williams; Judith A West-Mays Journal: Dis Model Mech Date: 2016-06-23 Impact factor: 5.758