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Sydney Green, Suneel Gupta, Prashant R. Sinha, Nishant Rajiv Sinha, Praveen Balne, Nathan Hesemann, Shyam S Chaurasia, Rajiv R Mohan; Role of Smad3 in healing cornea using knockout (Smad3-/-) mice. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2610.
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Excessive proliferation and transdifferentiation of corneal stromal fibroblasts causes haze/fibrosis in the cornea. TGFβ plays key role in corneal repair and fibrosis, and relays its signal through Smad pathway. We sought to study the effects of Smad3 knockdown in corneal repair and fibrosis in vivo using Smad3-/- and Smad3+/+ mice and alkali wounding model.
Smad3+/+ and Smad3-/- strains of 129-SMad3tm1Par were used. Corneal injury was created with alkali in mice to study the role of Smad3 in corneal repair. Slit-lamp microscopy, stereo-microscopy were used to record ocular health and corneal haze in live animals. H&E was used to study morphological alterations. Real-time qRT-PCR and immunohistochemistry were used to measure changes in profibrotic genes mRNA and protein levels.
Slitlamp clinical exams and stereo-microscopy detected notably less opaque cornea in the eyes of Smad3-/- mice compared to the Smad3+/+ until 21 days (p<0.01) in live animals. Corneal tissue sections of Smad3-/- mice showed significantly less αSMA+ cells compared to corneas of the wild type, Smad3+/+ animals (p< 0.05). corneas of the Smad3-/- mice showed significantly less mRNA levels of pro-fibrotic genes, α-smooth muscle actin (α-SMA), fibronectin, collagen III and f-actin (p<0.05, p<0.01, or p<0.001). Ongoing studies of Smad3+/+ and Smad3-/- mouse corneas show alterations in Wnt and β-catenin mRNA and protein levels.
Removal of Smad3 does not fully block TGFβ signaling and haze formation in the cornea in vivo. There appears a possibility of a crosstalk between TGFβ/Smad3 and Wnt/β-catenin canonical pathways.
This is a 2020 ARVO Annual Meeting abstract.
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