Fink, None; S.S. Schirmer’s test, epithelium-stroma Rabbit Polyclonal to GHITM separation, and corneal edema. TED mitigated clinical symptoms by reducing corneal edema, Fantes scores, CCT, and Schirmer’s test. Further, TED decreased SM-induced corneal haze, inflammatory and profibrotic markers, transforming growth factorCTGF-1 and cyclooxygenase-2COX-2, and damage to corneal structure, including epithelial-stromal integrity. Conclusions The developed multimodal PFI-3 eyedrop formulation, TED, has potential to mitigate acute MGK effectively in vivo. Translational Relevance TED is effective against MGK 0.05 were considered statistically significant. The sample size was determined using the G*Power (188.8.131.52 software, www.psycho.uni-duesseldorf.de/abteilungen/aap/gpower3) priori power analysis method to achieve = 0.05; PFI-3 power 0.9. Results Fluorescein dye staining The fluorescein dye test demonstrated no corneal epithelial erosion/defect or loss of epithelial barrier function in naive and TED-only treated rabbit eyes at day-3 (Figs.?1A,?1B) and day-7 (Figs.?1E,?1F). This revealed that the TED dose administered was acceptable and safe PFI-3 to rabbit eye. On the other hand, SM vapor exposure to rabbit eyes caused significant corneal epithelial erosion/defect at day-3 (Fig.?1C; naive vs. SM, 0.0001), which continued at day-7 (Fig.?1G; naive vs. SM, = 0.0002). TED dosing to the SM-exposed rabbit PFI-3 eyes significantly mitigated corneal epithelial erosion and loss of barrier function at day-3 (Fig.?1D; SM vs. SM+TED, = 0.0001) and day-7 (Fig.?1H; SM vs. SM+TED, = 0.0337). Quantification of corneal epithelial erosion/defect in rabbit corneal sections was performed digitally for each of the four groups. At day-3, measurements were as follows: naive = 0 pixel (Fig.?1A), TED-only = 0 pixel (Fig.?1B), SM = 205,852 25,310 pixels (Fig.?1C), and SM+TED = 74,189 11,086 pixels (Fig.?1D). At day-7, measurements were as follows: naive = 0 (Fig.?1E), TED-only = 0 (Fig.?1F), SM = 132,239 30,710 pixels, and SM+TED = 58,142 11,484 pixels. Open in a separate window Figure 1. Representative fluorescein dye test images showing the extent/area of corneal epithelial erosion/defect in rabbit eyes. SM-vapor severely damaged corneal epithelium at day-3 (C, 0.0001). Eyes that received TED dosing post-SM exposure exhibited notable reduction in corneal haze (SM vs. SM+TED) at day-3 (= 0.0344) and day-7 (= 0.0014) (Fig.?4) in this pilot study. Open in a separate window Figure 4. Quantification of mean corneal haze using the Fantes score in naive, TED, SM, and SM+TED. The corneal haze score was significantly increased in rabbit eyes after SM exposure compared to the naive and decreased in the SM+TED as compared to the SM exposure at day-3, and day-7. The TED alone treatment to the cornea did not cause corneal haze and scored 0.00 at the Fantes scale. Results are expressed as Mean SEM (**** 0.0001 **= 0.0014, and *= 0.0344, One-way ANOVA). Histopathological Evaluation The histological H&E staining demonstrated normal corneal anatomical features in the untreated naive (Figs.?5A,?5E) and topical TED-only administered rabbit eyes (Figs.?5B,?5F). A lack of detectable corneal epithelial damage or ocular edema in TED-only administered eyes at day-3 (Fig.?5B) or day-7 (Fig.?5F) implied that the tested TED dose was harmless to rabbit eyes. The histological H&E staining of SM vapor-exposed rabbit eyes exhibited dramatic corneal edema at day-3 (Fig.?5C; naive vs. SM, = 0.0049), which continued to the PFI-3 same.