June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Role of Smad3 in healing cornea using knockout (Smad3-/-) mice
Author Affiliations & Notes
  • Sydney Green
    College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States
  • Suneel Gupta
    Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri, United States
    College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States
  • Prashant R. Sinha
    Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri, United States
    College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States
  • Nishant Rajiv Sinha
    Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri, United States
    College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States
  • Praveen Balne
    Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri, United States
    College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States
  • Nathan Hesemann
    Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri, United States
    College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States
  • Shyam S Chaurasia
    College of Veterinary Medicine, University of Missouri, Columbia, Missouri, United States
  • Rajiv R Mohan
    Harry S. Truman Memorial Veteran Hospital, Columbia, Missouri, United States
    Mason Eye Institute and VMTH, University of Missouri, Columbia, Missouri, United States
  • Footnotes
    Commercial Relationships   Sydney Green, None; Suneel Gupta, None; Prashant Sinha, None; Nishant Sinha, None; Praveen Balne, None; Nathan Hesemann, None; Shyam Chaurasia, None; Rajiv Mohan, None
  • Footnotes
    Support  NEI/NIH R01EY030774 and RO1EY17294, VA Merit 1I01BX000357 and Ruth Kraeuchi Missouri Endowed Chair Ophthalmology Fund
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2610. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      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.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×