Coenzyme Q10 instilled as eye drops on the cornea reaches the retina and protects retinal layers from apoptosis in a mouse model of kainate-induced retinal damage

Invest Ophthalmol Vis Sci. 2012 Dec 17;53(13):8295-302. doi: 10.1167/iovs.12-10374.

Abstract

Purpose: To evaluate if coenzyme Q10 (CoQ10) can protect retinal ganglion cells (RGCs) from apoptosis and, when instilled as eye drops on the cornea, if it can reach the retina and exert its antiapoptotic activity in this area in a mouse model of kainate (KA)-induced retinal damage.

Methods: Rat primary or cultured RGCs were subjected to glutamate (50 μM) or chemical hypoxia (Antimycin A, 200 μM) or serum withdrawal (FBS, 0.5%) in the presence or absence of CoQ10 (10 μM). Cell viability was evaluated by light microscopy and fluorescence-activated cell sorting analyses. Apoptosis was evaluated by caspase 3/7 activity and mitochondrion depolarization tetramethylrhodamine ethyl ester analysis. CoQ10 transfer to the retina following its instillation as eye drops on the cornea was quantified by HPLC. Retinal protection by CoQ10 (10 μM) eye drops instilled on the cornea was then evaluated in a mouse model of KA-induced excitotoxic retinal cell apoptosis by cleaved caspase 3 immunohistofluorescence, caspase 3/7 activity assays, and quantification of inhibition of RGC loss.

Results: CoQ10 significantly increased viable cells by preventing RGC apoptosis. Furthermore, when topically applied as eye drops to the cornea, it reached the retina, thus substantially increasing local CoQ10 concentration and protecting retinal layers from apoptosis.

Conclusions: The ability of CoQ10 eye drops to protect retinal cells from apoptosis in the mouse model of KA-induced retinal damage suggests that topical CoQ10 may be evaluated in designing therapies for treating apoptosis-driven retinopathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Antimycin A / analogs & derivatives
  • Antimycin A / toxicity
  • Apoptosis / drug effects*
  • Caspase 3
  • Caspase 7 / metabolism
  • Cell Count
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Cornea / metabolism*
  • Disease Models, Animal*
  • Dose-Response Relationship, Drug
  • Fluorescent Antibody Technique, Indirect
  • Glutamic Acid / toxicity
  • Kainic Acid / toxicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / metabolism
  • Ophthalmic Solutions / administration & dosage
  • Ophthalmic Solutions / pharmacokinetics
  • Ophthalmic Solutions / pharmacology
  • Rabbits
  • Rats
  • Rats, Wistar
  • Retina / metabolism*
  • Retinal Diseases / chemically induced
  • Retinal Diseases / metabolism
  • Retinal Diseases / pathology
  • Retinal Diseases / prevention & control*
  • Retinal Ganglion Cells / drug effects
  • Retinal Ganglion Cells / metabolism
  • Retinal Ganglion Cells / pathology
  • Time Factors
  • Ubiquinone / administration & dosage
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / pharmacokinetics
  • Ubiquinone / pharmacology
  • Vitamins / administration & dosage
  • Vitamins / pharmacokinetics
  • Vitamins / pharmacology

Substances

  • Ophthalmic Solutions
  • Vitamins
  • antimycin
  • Ubiquinone
  • Glutamic Acid
  • Antimycin A
  • Casp3 protein, rat
  • Caspase 3
  • Caspase 7
  • coenzyme Q10
  • Kainic Acid