Abstract
Purpose :
Our previous studies indicating that the ablation of the TGFb receptors and Smad4 can cause the Corneal Ectasia (CE)-like pathological stroma thinning to different levels, in which the Smad4 exhibited the mildest phenotype. This study is to elucidate whether Smad4 together with Yap and Taz can serve as novel molecular targets to intervene the pathological thinning.
Methods :
To elucidate whether Smad4, Yap and Taz can serve as molecular targets to intervene the pathological thinning, multi-transgene mouse lines including KRrt/TC/Tgfbr1flox/flox/Smad4flox/flox, KRrt/TC/Tgfbr2flox/flox/Smad4flox/flox, KRrt/TC/Tgfbr1flox/flox/Yapflox/flox/Tazflox/flox, KRrt/TC/Tgfbr2flox/flox/Yapflox/flox/Tazflox/flox, KRrt/TC/ Yapflox/flox/Tazflox/flox were used in the research. The effect genes are designed to knockout from the corneal stroma at embryonic and postnatal stages. The OCT, OCE, HE, immunostaining and TEM were used to monitor the ectasia progression, tissue density, tissue histological changes, cell behaviors and protein level changes.
Results :
OCT revealed that double-knockout and triple-knockout of “Tgfbr1 and Smad4”, “Tgfbr2 and Smad4”, “Tgfbr1, Yap and Taz” and “Tgfbr2, Yap and Taz” can prevent the pathological thinning found in the Tgfbr1kera-cko and Tgfbr2kera-cko mice. Histology indicating that the corneal stroma thickness increased in “intervene group” compared to those in littermate control. Immunostaining showed that the cell fate and the behavior were not altered between two groups. OCE indicating the stiffness increased in intervene group.
Conclusions :
Smad4, Yap and Taz can serve as novel molecular targets to intervene pathological corneal stroma thinning found in TGFb signaling deficiency mouse lines.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.