Topical 0.1% NorLeu3Angiotensin(1-7) significantly decreased corneal haze and increased keratocyte density (p < 0.05) following severe corneal trauma in rabbits.
Does topical NorLeu3Angiotensin(1-7) improve corneal healing and reduce fibrosis in rabbits with full-thickness corneal lacerations?
Topical NorLeu3Angiotensin(1-7) reduces myofibroblast activity and fibrosis following severe corneal trauma in a rabbit model.
p-value: p=<0.05
Severe full-thickness corneal lacerations disrupt the tight cellular and extracellular matrix (ECM) organization required for corneal transparency. Following injury, an influx of transforming growth factor beta (TGFβ) into the corneal stroma signals the formation of haze-inducing myofibroblasts, resulting in excessive stromal remodeling and corneal haze. We hypothesized that MasR activation using NorLeu3Angiotensin (1-7) (NLE) engages the pro-resolving arm of the renin–angiotensin system (RAS) to minimize fibrotic corneal repair. In this study, 6 mm stellate-shaped, full-thickness corneal lacerations were induced in New Zealand Black (NZB) rabbits and treated with topical vehicle, or 0.1%, 0.3%, or 0.45% NLE. Corneal healing was evaluated using noninvasive corneal imaging, histology, and the gene expression of RAS- and fibrosis-related targets (MasR, AT1R, TGFβR1). Corneal imaging revealed significantly decreased corneal haze (p < 0.05) and increased keratocyte density with 0.1% NLE treatment (p < 0.05). Immunofluorescence showed significantly reduced α-smooth muscle actin (αSMA), indicating decreased myofibroblast formation (p < 0.05). Additionally, 0.1% NLE reduced stromal TGFβR1, suggesting that NLE mediates its activity by disrupting the TGFβ/TGFβR axis. MasR and AT1R gene expression were downregulated, which contributes to a reduction in fibrosis. Collectively, these findings suggest that the NLE activation of MasR modulates RAS and TGFβ/TGFβR signaling to reduce myofibroblast activity and fibrosis following severe corneal trauma.
Chester et al. (Thu,) conducted a other in Severe full-thickness corneal lacerations. Topical NorLeu3Angiotensin(1-7) (NLE) vs. Topical vehicle was evaluated on Corneal healing evaluated by corneal haze, keratocyte density, and myofibroblast formation (p=<0.05). Topical 0.1% NorLeu3Angiotensin(1-7) significantly decreased corneal haze and increased keratocyte density (p < 0.05) following severe corneal trauma in rabbits.