Abstract
Purpose :
Alkali burns in the cornea lead fibrosis, angiogenesis and inflammation, leading to a significant loss of vision or blindness. This study was designed to investigate the inhibitory effect of recombinant protein decorin, and its delivery, when augmented with a cell penetrating peptide applied topically to the mouse cornea in vivo.
Methods :
Alkali burn was induced using 1N NaOH for 30 secs on the central part of the mouse cornea. Cell penetrating peptide (CPP) PODb was co-delivered with recombinant Decorin to the cornea topically. Mice were sacrificed after 7 days and eyes were analyzed using markers of angiogenesis (Iso-lectin), fibrosis (α-SMA), inflammation (CD45, F4/80) and apoptosis (TUNEL assay).
Results :
Alkali burn caused corneal opacity, robust angiogenesis and fibrosis in the cornea on day 7 after the injury. Topical application of decorin alone reduced corneal opacity, angiogenesis and fibrosis. However, use of PODb significantly enhanced the potency of decorin. Alkali burn also activated the innate immune system as measured by infiltration of CD45+ and F4/80+ cells, which were greatly diminished by the application of Decorin when coupled with PODb. Furthermore, we also noted a significant reduction in TUNEL positive cells in Decorin-treated mice with PODb compared to Decorin alone.
Conclusions :
Decorin has a protective effect on corneal fibrosis and angiogenesis. It also regulates the innate immune system and apoptosis in the cornea post alkali burn. PODb improves the therapeutic efficacy and potency of Decorin, suggesting that it facilitates topical uptake of decorin by the injured cornea.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.