title: Effect of Topical 5-Aminoimidazole-4-carboxamide-1-β-d-Ribofuranoside in a Mouse Model of Experimental Dry Eye.
abstract: OBJECTIVE
  To investigate the efficacy of topical 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) in a mouse model of experimental dry eye (EDE).
  
  
  METHODS
  Eye drops consisting of 0.001% or 0.01% AICAR, 0.05% cyclosporine A (CsA), or balanced salt solution (BSS) were applied for the treatment of EDE. Tear volume, tear film break-up time (BUT), and corneal fluorescein staining scores were measured 10 days after treatment. Levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interferon gamma-induced protein 10 (IP-10), and monokine induced by interferon-γ (MIG) were measured in the conjunctiva. In addition, Western blot, periodic acid-Schiff staining for evaluating goblet cell density, flow cytometry for counting the number of CD4+CXCR3+ T cells, and immunohistochemistry for detection of 4-hydroxy-2-nonenal (4HNE) were performed.
  
  
  RESULTS
  Mice treated with 0.01% AICAR showed a significant improvement in all clinical parameters compared with the EDE control, vehicle control, and 0.001% AICAR groups (P < 0.001). A significant decrease in the levels of IL-1β, IL-6, TNF-α, IFN-γ, IP-10, and MIG, the number of CD4+CXCR3+ T cells, and the number of 4HNE-positive cells were also observed in the 0.01% AICAR group (P < 0.001). Although 0.05% CsA also led to an improvement in clinical parameters and inflammatory molecule levels, its therapeutic effects were comparable or inferior to those of 0.01% AICAR.
  
  
  CONCLUSIONS
  Topical application of 0.01% AICAR can markedly improve clinical signs and decrease inflammation in the ocular surface of EDE, suggesting that AICAR eye drops may be used as a therapeutic agent for dry eye disease.
authors.affiliation: Department of Ophthalmology and Research Institute of Medical Sciences Chonnam National University Medical School and Hospital, Gwangju, Korea.
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Sung
authors.affiliation: Department of Ophthalmology and Research Institute of Medical Sciences Chonnam National University Medical School and Hospital, Gwangju, Korea 2Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiame.
authors.forename: Zhengri
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Ophthalmology and Research Institute of Medical Sciences Chonnam National University Medical School and Hospital, Gwangju, Korea.
authors.forename: Lian
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Ophthalmology and Research Institute of Medical Sciences Chonnam National University Medical School and Hospital, Gwangju, Korea.
authors.forename: Ji Suk
authors.initials: JS
authors.lastname: Choi
authors.affiliation: Department of Ophthalmology and Research Institute of Medical Sciences Chonnam National University Medical School and Hospital, Gwangju, Korea.
authors.forename: Won
authors.initials: W
authors.lastname: Choi
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
authors.forename: Min Jung
authors.initials: MJ
authors.lastname: Park
authors.affiliation: College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Ophthalmology and Research Institute of Medical Sciences Chonnam National University Medical School and Hospital, Gwangju, Korea.
authors.forename: Kyung Chul
authors.initials: KC
authors.lastname: Yoon
mesh_terms: D000287:Administration, Topical; D000447:Aldehydes / Q000378:metabolism; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D054370:Chemokine CXCL9 / Q000378:metabolism; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009883:Ophthalmic Solutions; D012265:Ribonucleotides / Q000494:pharmacology*; D013666:Tears / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000447:Aldehydes; D054370:Chemokine CXCL9; D007004:Hypoglycemic Agents; D053583:Interleukin-1beta; D009883:Ophthalmic Solutions; D012265:Ribonucleotides; D014409:Tumor Necrosis Factor-alpha; D000620:Aminoimidazole Carboxamide; D007371:Interferon-gamma; C031143:AICA ribonucleotide; C027576:4-hydroxy-2-nonenal