Free-Radical Scavenger NSP-116 Protects the Corneal Epithelium against UV-A and Blue LED Light Exposure

Biol Pharm Bull. 2021;44(7):937-946. doi: 10.1248/bpb.b21-00017.

Abstract

The corneal epithelium is continuously exposed to oxygen, light, and environmental substances. Excessive exposure to those stresses is thought to be a risk factor for eye diseases. Photokeratitis is damage to the corneal epithelium resulting in a painful eye condition caused by unprotected exposure to UV rays, usually from sunlight, and is often found in people who spend a long time outdoors. In modern life, human eyes are exposed to artificial light from light-emitting diode (LED) displays of computers and smartphones, and it has been shown that short-wavelength (blue) LED light can damage eyes, especially photoreceptors. However, the effect of blue LED light on the cornea is less understood. In addition, it is important to develop new treatments for preserving human eyesight and eye health from light stress. Here, we used human corneal epithelial cells-transformed (HCE-T) cells as an in-vitro model to investigate the protective effect of NSP-116, an imidazolyl aniline derivative, against the oxidative stress induced by light in the corneal epithelium. Treatment with 10 µM NSP-116 significantly increased the cell viability and reduced the death ratio following UV or blue LED light exposure. Furthermore, NSP-116 treatment decreased light-induced reactive oxygen species production and preserved the mitochondrial membrane potential. Immunoblotting data showed that NSP-116 suppressed the stress response pathway. Finally, NSP-116 treatment prevented corneal epithelial apoptosis induced by blue LED light in an in-vivo mouse model. In conclusion, NSP-116 has a protective effect against oxidative stress and corneal cell death from both UV and blue LED light exposure.

Keywords: NSP-116; UV ray; blue light-emitting diode light; human corneal epithelium cells-transformed; reactive oxygen species.

MeSH terms

  • Aniline Compounds / pharmacology
  • Aniline Compounds / therapeutic use*
  • Animals
  • Cell Death / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Corneal Injuries / drug therapy*
  • Corneal Injuries / pathology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / physiology
  • Epithelium, Corneal / drug effects*
  • Epithelium, Corneal / pathology
  • Epithelium, Corneal / radiation effects*
  • Free Radical Scavengers / pharmacology
  • Free Radical Scavengers / therapeutic use*
  • Humans
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use*
  • Light / adverse effects*
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Radiation Injuries, Experimental / drug therapy*
  • Radiation Injuries, Experimental / pathology
  • Radiation-Protective Agents / pharmacology
  • Radiation-Protective Agents / therapeutic use*
  • Reactive Oxygen Species / metabolism

Substances

  • 4-(4-acetylpiperazin-1-yl)-2-(1H-imidazol-1-yl)aniline
  • Aniline Compounds
  • Free Radical Scavengers
  • Imidazoles
  • Radiation-Protective Agents
  • Reactive Oxygen Species