Activation of Apoptosis in a βB1-CTGF Transgenic Mouse Model |
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Authors: | Maximilian Weiss Sabrina Reinehr Ana M Mueller-Buehl Johanna D Doerner Rudolf Fuchshofer Gesa Stute H Burkhard Dick Stephanie C Joachim |
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Affiliation: | 1.Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany; (M.W.); (S.R.); (A.M.M.-B.); (J.D.D.); (G.S.); (H.B.D.);2.Institute of Human Anatomy and Embryology, University Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany; |
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Abstract: | To reveal the pathomechanisms of glaucoma, a common cause of blindness, suitable animal models are needed. As previously shown, retinal ganglion cell and optic nerve degeneration occur in βB1-CTGF mice. Here, we aimed to determine possible apoptotic mechanisms and degeneration of different retinal cells. Hence, retinae were processed for immunohistology (n = 5–9/group) and quantitative real-time PCR analysis (n = 5–7/group) in 5- and 10-week-old βB1-CTGF and wildtype controls. We noted significantly more cleaved caspase 3+ cells in βB1-CTGF retinae at 5 (p = 0.005) and 10 weeks (p = 0.02), and a significant upregulation of Casp3 and Bax/Bcl2 mRNA levels (p < 0.05). Furthermore, more terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL+) cells were detected in transgenic mice at 5 (p = 0.03) and 10 weeks (p = 0.02). Neurofilament H staining (p = 0.01) as well as Nefh (p = 0.02) and Tubb3 (p = 0.009) mRNA levels were significantly decreased at 10 weeks. GABAergic synapse intensity was lower at 5 weeks, while no alterations were noted at 10 weeks. The glutamatergic synapse intensity was decreased at 5 (p = 0.007) and 10 weeks (p = 0.01). No changes were observed for bipolar cells, photoreceptors, and macroglia. We conclude that apoptotic processes and synapse loss precede neuronal death in this model. This slow progression rate makes the βB1-CTGF mice a suitable model to study primary open-angle glaucoma. |
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Keywords: | β B1-CTGF primary open-angle glaucoma apoptosis caspase 3 neurofilament H Bax/Bcl2 synapse |
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