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J. V. Robertson, M. Duong, K. Kazlovskis, A. K. Ball, J. A. West-Mays; Mice Overexpressing TGFβ in the Eye Develop Features Similar to Primary Closed Angle Glaucoma. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5108. doi: https://doi.org/.
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Transforming growth factor beta (TGFβ) is known to be involved in the progression of fibrosis. Anecdotal evidence suggests that TGFβ may be a key player in the development of glaucoma, however little is known about its specific role(s). To study its involvement in glaucomatous pathology, we have employed the use of mice over-expressing active TGFβ in the lens.
Transgene expression of active TGFβ in these mice is controlled by the αA-crystallin promoter, which targets transgene expression to the lens (J. Clin. Invest. 101: 625-634,1998). Transgenic and wildtype littermates aged from 1 month to over 5 months were used. IOP was measured using the Tonolab rebound tonometer. Animals were sacrificed, enucleated and globes were fixed for morphometric analyses. Eyes were processed and paraffin sectioned for routine histology. Immunolocalization was performed to detect αSMA, a marker of fibrosis and TUNEL, a marker of apoptosis.
At 1 month of age, mice over-expressing TGFβ had a significantly (1) higher IOP, (2) larger globe size, (3) smaller optic nerve diameter and (4) fewer RGCs compared to wildtype littermates. Moreover, progressive retinal degeneration and formation of peripheral anterior synechiae occured in the TGFβ transgenic mice over the time period examined whereas these features were absent in wildtype littermates. Fibrosis in TGFβ transgenic mice was characterized by the presence of αSMA staining in all retinal cell layers except for the RGC layer. Wildtype littermates did not express αSMA in the retina at any time. TUNEL staining throughout the retinal layers indicated abundant apoptosis occurring in TGFβ transgenic animals, whereas wildtype littermates demonstrated no TUNEL staining.
Together these results demonstrate that mice over-expressing active TGFβ in the lens develop features similar to human closed angle glaucoma. This animal model may therefore be an important genetic tool for studying the development and mechanisms of TGFβ induced primary closed angle glaucoma.
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