Gebert, Magdalena and Heimbucher, Johanna and Gsell, Valentina K. and Keimer, Kristof and Dillinger, Andrea E. and Tamm, Ernst R. (2024) Induced Attenuation of Scleral TGF-β Signaling in Mutant Mice Increases Susceptibility to IOP-Induced Optic Nerve Damage. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 65 (1): 48. ISSN 0146-0404, 1552-5783
Full text not available from this repository. (Request a copy)Abstract
Purpose: Axonal optic nerve (ON) damage in glaucoma is characteristically associated with increased amounts of active transforming growth factor-beta 2 (TGF-beta 2) in the ON head. Here we investigated the functional role of scleral TGF-beta signaling in glaucoma. Methods: A deficiency of Tgfbr2, which encodes for TGF-beta receptor type II (TGF-beta RII), the essential receptor for canonical TGF-beta signaling, was induced in fibroblasts (including those of the sclera) of mutant mice. To this end, 5-week-old mice were treated with tamoxifen eye drops. Experimental glaucoma was induced in 8-week-old mice using a magnetic microbead (MB) model. After 6 weeks of high intraocular pressure (IOP), the ON axons and their somata in the retina were labeled by paraphenylenediamine (PPD) and RNA-binding protein with multiple splicing (RBPMS) immunohistochemistry, respectively, and quantified. Results: Tamoxifen treatment resulted in a significant decrease of TGF-beta RII and its mRNA in the sclera. After 6 weeks of high IOP, reduced numbers of PPD-stained ON axons were seen in MB-injected eyes in comparison with not-injected contralateral eyes. Moreover, MB injection also led to a decrease of retinal ganglion cell (RGC) somata as seen in RBPMS-stained retinal wholemounts. Axon loss and RGC loss were significantly higher in mice with a fibroblast specific deficiency of TGF-beta RII in comparison with control animals. Conclusions: We conclude that the ablation of scleral TGF-beta signaling increases the susceptibility to IOP-induced ON damage. Scleral TGF-beta signaling in mutant mice appears to be beneficial for ON axon survival in experimentally induced glaucoma.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR-BETA; OCULAR HYPERTENSION TREATMENT; OPEN-ANGLE GLAUCOMA; EXTRACELLULAR-MATRIX; LATENT TGF-BETA-1; RECOMBINATION; EXPRESSION; MOLECULE; DELETION; COLLAGEN; sclera; TGF-beta signaling; experimental glaucoma; optic nerve; retinal ganglion cells |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Humananatomie und Embryologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Jul 2025 07:34 |
| Last Modified: | 17 Jul 2025 07:34 |
| URI: | https://pred.uni-regensburg.de/id/eprint/63604 |
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