The Favorable Effect of Mesenchymal Stem Cell Treatment on the Antioxidant Protective Mechanism in the Corneal Epithelium and Renewal of Corneal Optical Properties Changed after Alkali Burns

Abstract

The aim of this study was to examine whether mesenchymal stem cells (MSCs) and/or corneal limbal epithelial stem cells (LSCs) influence restoration of an antioxidant protective mechanism in the corneal epithelium and renewal of corneal optical properties changed after alkali burns. The injured rabbit corneas (with 0.25 N NaOH) were untreated or treated with nanofiber scaffolds free of stem cells, with nanofiber scaffolds seeded with bone marrow MSCs (BM-MSCs), with adipose tissue MSCs (Ad-MSCs), or with LSCs. On day 15 following the injury, after BM-MSCs or LSCs nanofiber treatment (less after Ad-MSCs treatment) the expression of antioxidant enzymes was restored in the regenerated corneal epithelium and the expressions of matrix metalloproteinase 9 (MMP9), inducible nitric oxide synthase (iNOS), α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and vascular endothelial factor (VEGF) were low. The central corneal thickness (taken as an index of corneal hydration) increased after the injury and returned to levels before the injury. In injured untreated corneas the epithelium was absent and numerous cells revealed the expressions of iNOS, MMP9, α-SMA, TGF-β1, and VEGF. In conclusion, stem cell treatment accelerated regeneration of the corneal epithelium, restored the antioxidant protective mechanism, and renewed corneal optical properties.

Molecular Hydrogen Effectively Heals Alkali-Injured Cornea via Suppression of Oxidative Stress

“…H 2 has no cytotoxicity even at high concentration [10]. It quickly penetrates through tissues and cells and suppresses oxidative stress occurring in the anterior eye segment immediately after the injury, such as alkali burns or UVB irradiation [1–7]. After corneal injuries, the imbalance between antioxidants and prooxidants appeared in the cornea, resulting in oxidative stress.…”

“…Immediately after corneal injury, such as alkali burns or irradiation of the cornea with UVB rays, oxidative stress appears in the cornea [1–7]. The activities as well as expressions of corneal antioxidant enzymes substantially decrease, whereas the activities of prooxidant enzymes (e.g., oxidases that generate reactive oxygen species, ROS) remain at physiological levels or even increase.…”

Subconjunctival bone marrow‐derived mesenchymal stem cell therapy as a novel treatment alternative for equine immune‐mediated keratitis: A case series

“…Autologous bone marrow‐derived mesenchymal stem cells (BM‐MSCs) and allogeneic adipose‐derived MSCs have been used in equine practice with encouraging outcomes for the treatment and repair of a variety of inflammatory and traumatic musculoskeletal injuries including tendonitis and intra‐articular disease such as meniscal injuries and osteoarthritis . Ocular therapeutic benefits of functionally viable MSC therapy have also been documented . MSCs have been shown to accelerate corneal wound healing, decrease oxidative stress, and suppress proinflammatory cytokine profiles resulting in decreased opacification and neovascularization of an injured corneal surface in rabbit models …”

“…Ocular therapeutic benefits of functionally viable MSC therapy have also been documented . MSCs have been shown to accelerate corneal wound healing, decrease oxidative stress, and suppress proinflammatory cytokine profiles resulting in decreased opacification and neovascularization of an injured corneal surface in rabbit models …”

“…[12][13][14] Ocular therapeutic benefits of functionally viable MSC therapy have also been documented. [15][16][17][18][19] MSCs have been shown to accelerate corneal wound healing, decrease oxidative stress, and suppress proinflammatory cytokine profiles resulting in decreased opacification and neovascularization of an injured corneal surface in rabbit models. 15,16 Given their ability to decrease surface inflammation and opacification, MSCs may play an important therapeutic role in the treatment of equine IMMK.…”