Abstract
Purpose :
Chemical injury to the eye leads to ocular hypoxia and inflammation, which in turn contribute to tissue damage and decrease in vision. We have previously demonstrated that a perfluorodecalin-based supersaturated oxygen emulsion (SSOE) reduces optical opacity and tissue fibrosis after alkali burn to mouse corneas. Herein, we aim to determine the effects of SSOE on ocular hypoxia and tissue inflammation after alkali burn.
Methods :
SSOE containing 25% oxygen-carrier perfluorodecalin was manufactured in hyperbaric condition. Alkali burn was induced by placing a 2-mm-diameter filter paper disc soaked with 1M sodium hydroxide solution onto the central cornea of BALB/C mouse for 20 seconds, followed by irrigation with PBS until the pH level of the ocular surface returned to 7. 50 μl SSOE or non-oxygenated emulsion (vehicle control) was applied to the cornea immediately after burn for 30 minutes. The anterior chamber oxygen concentration was recorded using the DP-PSt7-2 oxygen sensor. Cell apoptosis was determined with TUNEL staining. The expression of inflammatory markers IL-1β and MMP9 was determined with real-time PCR, and the infiltration of CD45+ cells to the cornea and conjunctiva was evaluated by immunostaining and flow cytometry, respectively.
Results :
Alkali burn led to a 60% decrease (165 vs 66 μmol/L, P<0.0001) in the anterior chamber oxygen concentration, which was reversed and further increased (535 μmol/L, almost 3 times over atmospheric level) by topical application of SSOE, but not the vehicle control. Alkali burn led to cell apoptosis in all layers of the cornea at 1 hour, whereas in SSOE-treated eyes, apoptotic cells were only seen at the superficial epithelial layer (TUNEL-positive cell 100% in control vs 45% in SSOE group, P=0.025). Moreover, SSOE reduced apoptosis of lens epithelial cells (60% in control vs 17% in SSOE group, P=0.004). SSOE treatment reduced the expression of IL-1β in the cornea (P=0.003) and of MMP9 in the iris/ciliary body (P=0.049). In addition, SSOE treatment decreased the infiltration of CD45+ inflammatory cells in the cornea and conjunctiva (27.8% in control vs 19.9% in SSOE group, P=0.002) at 24h after alkali burn.
Conclusions :
Topical application of SSOE reduces tissue hypoxia, cell apoptosis, and inflammation after alkali burn. These are the potential mechanisms underlying the therapeutic efficacy of SSOE in treating chemical injury.
This is a 2021 ARVO Annual Meeting abstract.