RESUMO
Purpose: Axonal optic nerve (ON) damage in glaucoma is characteristically associated with increased amounts of active transforming growth factor-beta 2 (TGF-ß2) in the ON head. Here we investigated the functional role of scleral TGF-ß signaling in glaucoma. Methods: A deficiency of Tgfbr2, which encodes for TGF-ß receptor type II (TGF-ßRII), the essential receptor for canonical TGF-ß 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-ßRII 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-ßRII in comparison with control animals. Conclusions: We conclude that the ablation of scleral TGF-ß signaling increases the susceptibility to IOP-induced ON damage. Scleral TGF-ß signaling in mutant mice appears to be beneficial for ON axon survival in experimentally induced glaucoma.
