title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Experimental Pathology and Oncology, University of Florence, Florence, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Lulli
authors.forename: Ewa
authors.initials: E
authors.lastname: Witort
authors.forename: Laura
authors.initials: L
authors.lastname: Papucci
authors.forename: Eugenio
authors.initials: E
authors.lastname: Torre
authors.forename: Christian
authors.initials: C
authors.lastname: Schipani
authors.forename: Christian
authors.initials: C
authors.lastname: Bergamini
authors.forename: Massimo
authors.initials: M
authors.lastname: Dal Monte
authors.forename: Sergio
authors.initials: S
authors.lastname: Capaccioli
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000968:Antimycin A / Q000031:analogs & derivatives / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D053179:Caspase 7 / Q000378:metabolism; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019084:Fluorescent Antibody Technique, Indirect; D018698:Glutamic Acid / Q000633:toxicity; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism*; D012164:Retinal Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D014815:Vitamins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D009883:Ophthalmic Solutions; D014815:Vitamins; C032456:antimycin; D014451:Ubiquinone; D018698:Glutamic Acid; D000968:Antimycin A; C505410:Casp3 protein, rat; D053148:Caspase 3; D053179:Caspase 7; C024989:coenzyme Q10; D007608:Kainic Acid