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Abstract #117079 Published in IGR 24-4
Induced Attenuation of Scleral TGF-β Signaling in Mutant Mice Increases Susceptibility to IOP-Induced Optic Nerve Damage
Gebert M; Heimbucher J; Gsell VK; Keimer K; Dillinger AE; Tamm ERInvestigative Ophthalmology and Visual Science 2024; 65: 48
PURPOSE: Axonal optic nerve (ON) damage in glaucoma is characteristically associated with increased amounts of active transforming growth factor-beta 2 (TGF-β2) in the ON head. Here we investigated the functional role of scleral TGF-β signaling in glaucoma. METHODS: A deficiency of Tgfbr2, which encodes for TGF-β receptor type II (TGF-βRII), the essential receptor for canonical TGF-β 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-βRII 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-βRII in comparison with control animals. CONCLUSIONS: We conclude that the ablation of scleral TGF-β signaling increases the susceptibility to IOP-induced ON damage. Scleral TGF-β signaling in mutant mice appears to be beneficial for ON axon survival in experimentally induced glaucoma.
Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
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