Activation of Apoptosis in a beta B1-CTGF Transgenic Mouse Model

Weiss, Maximilian and Reinehr, Sabrina and Mueller-Buehl, Ana M. and Doerner, Johanna D. and Fuchshofer, Rudolf and Stute, Gesa and Dick, H. Burkhard and Joachim, Stephanie C. (2021) Activation of Apoptosis in a beta B1-CTGF Transgenic Mouse Model. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 22 (4): 1997. ISSN , 1422-0067

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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 beta B1-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 beta B1-CTGF and wildtype controls. We noted significantly more cleaved caspase 3(+) cells in beta B1-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 beta B1-CTGF mice a suitable model to study primary open-angle glaucoma.

Item Type: Article
Uncontrolled Keywords: ; beta B1-CTGF; primary open-angle glaucoma; apoptosis; caspase 3; neurofilament H; Bax/Bcl2; synapse
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 13 Sep 2022 06:54
Last Modified: 13 Sep 2022 06:54
URI: https://pred.uni-regensburg.de/id/eprint/47259

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