Mechanisms of Stromal Fibrosis

Abstract

PurposeThis study was designed to uncover new drug targets to deal with the problems of fibrosis of the corneal stroma which can occur following an injury or infection, preventing the normal recovery of vision. Although, TGF‐β is clearly involved the detailed intracellular mechanisms necessary for a practical drug target are not available. The cellular target is the transition of the sessile keratocyte to a myofibroblast.MethodsCorneas of 8 week old C57BL6 mice underwent either an anterior keratectomy (AK) wound or infection with Pseudomonas aeruginosa (PA), and animals were sacrificed at 2 and 7 days, as well as 2 and 4 weeks after the procedures. The isolated stroma was used to monitor the expression and location of moesin, phospho‐moesin, TGF‐β1 and α‐SMA.ResultsTGF‐β1 and phospho‐moesin were not detected in normal corneal stromas. However, after either treatment, TGF‐β1 expression increased, along with phospho‐moesin and moesin in the wounded corneal stroma from day 2 to 7, and decreased after 2 weeks. No expression of TGF‐β1 and phospho‐moesin was found at PO week 4. Myofibroblasts positive for α‐SMA associated with either treatment were detected from day 2 to week 4 and peaked at week 2.ConclusionThese studies show that moesin interactions with actin fiber growth may be a focus drug development in fibrosis decreases; however, it remains to determine the exact details of that interaction.