Loss of retinal ganglion cells in a new genetic mouse model for primary open-angle glaucoma

Reinehr, Sabrina and Koch, Dennis and Weiss, Maximilian and Froemel, Franziska and Voss, Christina and Dick, H. Burkhard and Fuchshofer, Rudolf and Joachim, Stephanie C. (2019) Loss of retinal ganglion cells in a new genetic mouse model for primary open-angle glaucoma. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 23 (8). pp. 5497-5507. ISSN 1582-1838, 1582-4934

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Abstract

Primary open-angle glaucoma (POAG) is one of the most common causes for blindness worldwide. Although an elevated intraocular pressure (IOP) is the main risk factor, the exact pathology remained indistinguishable. Therefore, it is necessary to have appropriate models to investigate these mechanisms. Here, we analysed a transgenic glaucoma mouse model (ss B1-CTGF) to elucidate new possible mechanisms of the disease. Therefore, IOP was measured in ss B1-CTGF and wildtype mice at 5, 10 and 15 weeks of age. At 5 and 10 weeks, the IOP in both groups were comparable (P > 0.05). After 15 weeks, a significant elevated IOP was measured in ss B1-CTGF mice (P < 0.001). At 15 weeks, electroretinogram measurements were performed and both the a- and b-wave amplitudes were significantly decreased in ss B1-CTGF retinae (both P < 0.01). Significantly fewer Brn-3a(+) retinal ganglion cells (RGCs) were observed in the ss B1-CTGF group on flatmounts (P = 0.02), cross-sections (P < 0.001) and also via quantitative real-time PCR (P = 0.02). Additionally, significantly more cleaved caspase 3(+) RGCs were seen in the ss B1-CTGF group (P = 0.002). Furthermore, a decrease in recoverin(+) cells was observable in the ss B1-CTGF animals (P = 0.004). Accordingly, a significant down-regulation of Recoverin mRNA levels were noted (P < 0.001). Gfap expression, on the other hand, was higher in ss B1-CTGF retinae (P = 0.023). Additionally, more glutamine synthetase signal was noted (P = 0.04). Although no alterations were observed regarding photoreceptors via immunohistology, a significant decrease of Rhodopsin (P = 0.003) and Opsin mRNA (P = 0.03) was noted. We therefore assume that the ss B1-CTGF mouse could serve as an excellent model for better understanding the pathomechanisms in POAG.

Item Type: Article
Uncontrolled Keywords: INDUCED OCULAR HYPERTENSION; OPTIC-NERVE HEAD; INTRAOCULAR-PRESSURE; RISK-FACTORS; DBA/2J MICE; MULLER GLIA; PREVALENCE; ASTROCYTES; DAMAGE; INNER; electroretinogram; primary open-angle glaucoma; retinal ganglion cells; ss B1-CTGF
Subjects: 500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Anatomie
Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie
Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie > Prof. Dr. Ernst Tamm
Depositing User: Dr. Gernot Deinzer
Date Deposited: 02 Apr 2020 04:31
Last Modified: 02 Apr 2020 04:31
URI: https://pred.uni-regensburg.de/id/eprint/26521

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