Format

Send to

Choose Destination
Invest Ophthalmol Vis Sci. 2015 May;56(5):3149-58. doi: 10.1167/iovs.14-16153.

Effect of Topical 5-Aminoimidazole-4-carboxamide-1-β-d-Ribofuranoside in a Mouse Model of Experimental Dry Eye.

Author information

1
Department of Ophthalmology and Research Institute of Medical Sciences Chonnam National University Medical School and Hospital, Gwangju, Korea.
2
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.
3
College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.

Abstract

PURPOSE:

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.

PMID:
26024098
DOI:
10.1167/iovs.14-16153
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center