title: Effects of eye drops containing a mixture of omega-3 essential fatty acids and hyaluronic acid on the ocular surface in desiccating stress-induced murine dry eye.
abstract: OBJECTIVE
  To investigate the efficacy of the topical application of omega-3 essential fatty acids (EFAs) and hyaluronic acid (HA) mixtures in a mouse model of experimental dry eye (EDE).
  
  
  METHODS
  Eye drops consisting of 0.1% HA, 0.02%, or 0.2% omega-3 EFAs alone and mixture of 0.02%, or 0.2% omega-3 EFAs and 0.1% HA were applied in desiccating stress-induced murine dry eye. Corneal irregularity scores and fluorescein staining scores were measured 5 and 10 days after treatment. Levels of interleukin (IL)-1β, -17, and interferon gamma-induced protein (IP)-10 were measured in the conjunctiva at 10 days using a multiplex immunobead assay. The concentrations of hexanoyl-lys (HEL) and 4-hydroxynonenal (4-HNE) in conjunctiva tissue were measured with enzyme-linked immunosorbent assays.
  
  
  RESULTS
  Mice treated with the mixture containing 0.2% omega-3 EFAs showed a significant improvement in corneal irregularity scores and corneal fluorescein staining scores compared with EDE, HA, 0.02% or 0.2% omega-3 EFAs alone, and 0.02% omega-3 EFAs mixture-treated mice. A significant decrease in the levels of IL-1β, -17, and IP-10 were observed in the 0.2% EFAs mixture-treated group, compared with the other groups. In the mice treated with the mixture containing 0.2% omega-3 EFAs, the concentration of 4-HNE was also lower than the other groups. Although 0.2% omega-3 EFAs alone group also had a significant improvement in corneal irregularity scores and IL-17, IL-10, and 4 HNE levels compared with the other groups, the efficacy was lower than 0.2% omega-3 mixture group.
  
  
  CONCLUSIONS
  Topically applied eye drops containing a mixture of omega-3 EFAs and HA could improve corneal irregularity and corneal epithelial barrier disruption, and decrease inflammatory cytokines and oxidative stress markers on the ocular surface. Topical omega-3 EFAs and HA mixture may have a greater therapeutic effect on clinical signs and inflammation of dry eye compared with HA artificial tears.
authors.affiliation: Department of Ophthalmology, Chonnam National University Medical School and Hospital , Center for Creative Biomedical Scientists at Chonnam National University, Gwangju , Korea .
authors.forename: Zhengri
authors.initials: Z
authors.lastname: Li
authors.forename: Jung-Han
authors.initials: JH
authors.lastname: Choi
authors.forename: Han-Jin
authors.initials: HJ
authors.lastname: Oh
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Park
authors.forename: Jee-Bum
authors.initials: JB
authors.lastname: Lee
authors.forename: Kyung Chul
authors.initials: KC
authors.lastname: Yoon
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D054357:Chemokine CXCL10 / Q000378:metabolism; D003228:Conjunctiva / Q000187:drug effects* / Q000378:metabolism; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D003890:Desiccation; D004195:Disease Models, Animal; D004338:Drug Combinations; D015352:Dry Eye Syndromes / Q000188:drug therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D006820:Hyaluronic Acid / Q000494:pharmacology*; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL; D009883:Ophthalmic Solutions; D018384:Oxidative Stress
chemical_list: D000447:Aldehydes; D054357:Chemokine CXCL10; D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; D020381:Interleukin-17; D053583:Interleukin-1beta; D009883:Ophthalmic Solutions; D006820:Hyaluronic Acid; C027576:4-hydroxy-2-nonenal
keywords: Dry eye; eye drops; hyaluronic acid; mixtures; omega-3 essential fatty acids