Abstract
Purpose :
Beforely, we made Alk5 (type1 TGFb receptor) conditional knockout in the cornea stroma (cst), and showed Alk5 is related with proliferation and apoptosis of cornea (Yasuda et al. ARVO 2023). This Alk5Δ/Δcst mice which induced doxycycline (dox) from E0 showed thin cornea and penetrated at P18-21, so we can’t follow up it for a long term. Smad dependent pathway is important signal pathway of TGFb. We made Smad4Δ/Δcst mice to evaluated the long-term effects of TGFb signals on maintaining corneal homeostasis.
Methods :
Smad4Δ/Δcst mice were induced by dox from E0 or P0. A group of dox from E0 were compared with Alk5Δ/Δcst mice. A group of dox from P0 were induced to P180.
Results :
Alk5Δ/Δcst mice cornea were perforated P18-21. On the other hand, Smad4Δ/Δcst mice cornea were not perforated even P83. Smad4Δ/Δcst mice induced by dox P0-180 were developed Descemet's membrane detachment and inflammation and edema of the corneal stroma, similar to acute edema in keratoglobus patients.
Conclusions :
Smad4Δ/Δcst mice were able to be followed up for a long term, and had the potential to serve as an animal experimental model for keratoglobus, and future comparisons with human patient tissues are required.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.