Abstract
Purpose :
The fibrosis of the avascular central corneal stroma could result in vision loss. Gli1+ mesenchymal stem cells (MSC) were found to reside in the perivascular area and have the ability of self-renewal and fibrosis repair of heart, liver, lung or spinal cord, etc. This study explores the existence of Gli1+MSCs in the limbal stroma, and the role of Gli1+MSCs in fibrosis repairing of corneal injuries through lineage tracing.
Methods :
We sought to provide solid evidence of Gli1+ MSCs’ role in the process of corneal fibrosis healing in several procedures. In a corneal stroma wounding model using Gli1-CreERT2; tdTomato mice, Gli1+ MSCs’ cell fate is traced in the fibrosis healing process. Subconjunctival injection of the Gli1 activator, cyclopamine, and the inhibitor, GANT61, are applied to research the significance of Gli1+ cells in corneal fibrosis healing. Moreover, Gli1-CreERT2;iDTR-tdTomato mice are used to confirm the role of Gli1 by genetic deletion.
Results :
We observe Gli1+ cell fate in the corneal stroma both in homeostasis and during wound healing. Mosaic images of flattened corneas obtained by confocal microscopy show the expression of tdTomato after corneal injury at each time point. However, from one day to one year after the entire epithelium and central superficial corneal stromal injury, perivascular Gli1+ cells are significantly activated both in situ and move from the corneal limbus to the center to heal the injured cornea. Our results also show that inhibiting Gli1 could reduce corneal fibrosis but increase the healing time or the injury severity of the cornea.
Conclusions :
Gli1 progenitor cells mainly reside in the perivascular area of the corneal limbal stroma, but self-renew in the avascular corneal stroma in homeostasis. The activation of Gli1 increases the severity of corneal fibrosis while inhibition or deletion of Gli1 could reduce the fibrosis area but increase the healing time or the injury severity of the cornea. Thus, Gli1 could serve as a potential target for reducing injury-induced corneal fibrosis.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.