Activation of Apoptosis in a βB1-CTGF Transgenic Mouse Model.
Maximilian WeissSabrina ReinehrAna M Mueller-BuehlJohanna D DoernerRudolf FuchshoferGesa StuteH Burkhard DickStephanie Christine JoachimPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- cell death
- endoplasmic reticulum stress
- optic nerve
- mouse model
- oxidative stress
- signaling pathway
- gestational age
- metabolic syndrome
- clinical trial
- single cell
- cell proliferation
- adipose tissue
- optical coherence tomography
- stem cells
- bipolar disorder
- brain injury
- high resolution
- mesenchymal stem cells
- bone marrow
- cell therapy