| First Author | Mao M | Year | 2024 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 65 |
| Issue | 5 | Pages | 15 |
| PubMed ID | 38717426 | Mgi Jnum | J:348383 |
| Mgi Id | MGI:7640800 | Doi | 10.1167/iovs.65.5.15 |
| Citation | Mao M, et al. (2024) TGFbeta Signaling Dysregulation May Contribute to COL4A1-Related Glaucomatous Optic Nerve Damage. Invest Ophthalmol Vis Sci 65(5):15 |
| abstractText | PURPOSE: Mutations in the genes encoding type IV collagen alpha 1 (COL4A1) and alpha 2 (COL4A2) cause a multisystem disorder that includes ocular anterior segment dysgenesis (ASD) and glaucoma. We previously showed that transforming growth factor beta (TGFbeta) signaling was elevated in developing anterior segments from Col4a1 mutant mice and that reducing TGFbeta signaling ameliorated ASD, supporting a role for the TGFbeta pathway in disease pathogenesis. Here, we tested whether altered TGFbeta signaling also contributes to glaucoma-related phenotypes in Col4a1 mutant mice. METHODS: To test the role of TGFbeta signaling in glaucoma-relevant phenotypes, we genetically reduced TGFbeta signaling using mice with mutated Tgfbr2, which encodes the common receptor for all TGFbeta ligands in Col4a1+/G1344D mice. We performed slit-lamp biomicroscopy and optical coherence tomography for qualitative and quantitative analyses of anterior and posterior ocular segments, histological analyses of ocular tissues and optic nerves, and intraocular pressure assessments using rebound tonometry. RESULTS: Col4a1+/G1344D mice showed defects of the ocular drainage structures, including iridocorneal adhesions, and phenotypes consistent with glaucomatous neurodegeneration, including thinning of the nerve fiber layer, retinal ganglion cell loss, optic nerve head excavation, and optic nerve degeneration. We found that reducing TGFbeta receptor 2 (TGFBR2) was protective for ASD, ameliorated ocular drainage structure defects, and protected against glaucomatous neurodegeneration in Col4a1+/G1344D mice. CONCLUSIONS: Our results suggest that elevated TGFbeta signaling contributes to glaucomatous neurodegeneration in Col4a1 mutant mice. |
