Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 22, Issue 4, Pages -Publisher
MDPI
DOI: 10.3390/ijms22041997
Keywords
beta B1-CTGF; primary open-angle glaucoma; apoptosis; caspase 3; neurofilament H; Bax/Bcl2; synapse
Funding
- FoRUM (Ruhr-University Bochum, Germany)
- Ernst and Berta Grimmke foundation (Germany)
- Verein Gluck im Blick (Bochum, Germany)
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In this study, utilizing the βB1-CTGF mouse model to investigate the pathomechanisms of glaucoma revealed that apoptotic processes and synapse loss precede neuronal death in this model. The slow progression rate of degeneration in the βB1-CTGF mice makes them a suitable model for studying primary open-angle glaucoma.
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.
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