For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
23
views
40
references
 Top references
cited by
23
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      82
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Research on the Stability of a Rabbit Dry Eye Model Induced by Topical Application of the Preservative Benzalkonium Chloride

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Dry eye is a common disease worldwide, and animal models are critical for the study of it. At present, there is no research about the stability of the extant animal models, which may have negative implications for previous dry eye studies. In this study, we observed the stability of a rabbit dry eye model induced by the topical benzalkonium chloride (BAC) and determined the valid time of this model.

          Methods and Findings

          Eighty white rabbits were randomly divided into four groups. One eye from each rabbit was randomly chosen to receive topical 0.1% BAC twice daily for 2 weeks (Group BAC-W2), 3 weeks (Group BAC-W3), 4 weeks (Group BAC-W4), or 5 weeks (Group BAC-W5). Fluorescein staining, Schirmer's tests, and conjunctival impression cytology were performed before BAC treatment (normal) and on days 0, 7, 14 and 21 after BAC removal. The eyeballs were collected at these time points for immunofluorescence staining, hematoxylin and eosin (HE) staining, and electron microscopy. After removing BAC, the signs of dry eye in Group BAC-W2 lasted one week. Compared with normal, there were still significant differences in the results of Schirmer's tests and fluorescein staining in Groups BAC-W3 and BAC-W4 on day 7 ( P<0.05) and in Group BAC-W5 on day 14 ( P<0.05). Decreases in goblet cell density remained stable in the three experimental groups at all time points ( P<0.001). Decreased levels of mucin-5 subtype AC (MUC5AC), along with histopathological and ultrastructural disorders of the cornea and conjunctiva could be observed in Group BAC-W4 and particularly in Group BAC-W5 until day 21.

          Conclusions

          A stable rabbit dry eye model was induced by topical 0.1% BAC for 5 weeks, and after BAC removal, the signs of dry eye were sustained for 2 weeks (for the mixed type of dry eye) or for at least 3 weeks (for mucin-deficient dry eye).

          Related collections

          Most cited references40

          • Record: found
          • Abstract: found
          • Article: not found

          Preservatives in eyedrops: the good, the bad and the ugly.

          Christophe Baudouin, Antoine Labbe, Hong Liang … (2010)
          There is a large body of evidence from experimental and clinical studies showing that the long-term use of topical drugs may induce ocular surface changes, causing ocular discomfort, tear film instability, conjunctival inflammation, subconjunctival fibrosis, epithelial apoptosis, corneal surface impairment, and the potential risk of failure for further glaucoma surgery. Subclinical inflammation has also been described in patients receiving antiglaucoma treatments for long periods of time. However, the mechanisms involved, i.e., allergic, toxic, or inflammatory, as well as the respective roles of the active compound and the preservative in inducing the toxic and/or proinflammatory effects of ophthalmic solutions, is still being debated. The most frequently used preservative, benzalkonium chloride (BAK), has consistently demonstrated its toxic effects in laboratory, experimental, and clinical studies. As a quaternary ammonium, this compound has been shown to cause tear film instability, loss of goblet cells, conjunctival squamous metaplasia and apoptosis, disruption of the corneal epithelium barrier, and damage to deeper ocular tissues. The mechanisms causing these effects have not been fully elucidated, although the involvement of immunoinflammatory reactions with the release of proinflammatory cytokines, apoptosis, oxidative stress, as well as direct interactions with the lipid components of the tear film and cell membranes have been well established. Preservative-induced adverse effects are therefore far from being restricted to only allergic reactions, and side effects are often very difficult to identify because they mostly occur in a delayed or poorly specific manner. Care should therefore be taken to avoid the long-term use of preservatives, otherwise a less toxic alternative to BAK should be developed, as this weakly allergenic but highly toxic compound exerts dose- and time-dependent effects. On the basis of all these experimental and clinical reports, it would be advisable to use benzalkonium-free solutions whenever possible, especially in patients with the greatest exposure to high doses or prolonged treatments, in those suffering from preexisting or concomitant ocular surface diseases, and those experiencing side effects related to the ocular surface. Indeed, mild symptoms should not be underestimated, neglected, or denied, because they may very well be the apparent manifestations of more severe, potentially threatening subclinical reactions that may later cause major concerns. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
          Article 0 comments Cited 281 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface.

            Yu Luo, Amish Doshi, William J. Farley … (2004)
            To evaluate whether experimentally induced dry eye in mice activates mitogen-activated protein kinase (MAPK) signaling pathways, c-Jun N-terminal kinases (JNK), extracellular-regulated kinases (ERK), and p38 and stimulates ocular surface inflammation. 129SvEv/CD-1 mixed mice aged 6 to 8 weeks were treated with systemic scopolamine and exposure to an air draft for different lengths of time, from 4 hours to 10 days. Untreated mice were used as the control. The concentrations of IL-1beta and TNF-alpha in tear fluid washings and in corneal and conjunctival epithelia were measured by ELISA. MMP-9 in tear washings was evaluated by zymography, and gelatinase activity in the cornea and conjunctiva was determined by in situ zymography. Corneal and conjunctival epithelia were lysed in RIPA buffer for Western blot with MAPK antibodies, or they were lysed in 4 M guanidium thiocyanate solution for extraction of total RNA, which was used to determine gene expression by semiquantitative RT-PCR, real-time PCR, and gene array. Compared with those in age-matched control subjects, the concentrations of IL-1beta and MMP-9 in tear fluid washings and the concentrations of IL-1beta and TNF-alpha and gelatinolytic activity in the corneal and conjunctival epithelia were significantly increased in mice receiving treatments to induce dry eye after 5 or 10 days. The expression of IL-1beta, TNF-alpha, and MMP-9 mRNA by the corneal and conjunctival epithelia was also stimulated in mice treated for 5 or 10 days. The levels of phosphorylated JNK1/2, ERK1/2, and p38 MAPKs in the corneal and conjunctival epithelia were markedly increased as early as 4 hours after treatment, and they remained elevated up to 5 days. Experimental dry eye stimulates expression and production of IL-1beta, TNF-alpha, and MMP-9 and activates MAPK signaling pathways on the ocular surface. MAPKs are known to stimulate the production of inflammatory cytokines and MMPs, and they could play an important role in the induction of these factors that have been implicated in the pathogenesis of dry eye disease.
            Article 0 comments Cited 148 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Prevalence of dry eye among the elderly.

              OLIVER D. SCHEIN, BEATRIZ MUÑOz, JAMES M. TIELSCH … (1997)
              To study the demographics and estimate the prevalence of dry eye among elderly Americans. A population-based prevalence study was performed in 2,520 residents of Salisbury, Maryland, aged 65 years and older as of September 1993. The population was derived from the Health Care Financing Administration Medicare database. After completing a standardized questionnaire pertaining to dry eye symptoms, 2,420 subjects underwent Schirmer and rose bengal tests and anatomic assessment of the meibomian glands. In this population, 14.6% (363/2,482) were symptomatic, defined as reporting one or more dry eye symptoms often or all the time; 2.2% (53/2,448) were symptomatic and had a low Schirmer test result ( or = 5). Furthermore, 3.5% (84/2,425) were symptomatic and had either a low Schirmer score or a high rose bengal score, and 0.7% (17/2,420) were symptomatic and had both a low Schirmer score and a high rose bengal score. No association of symptoms or signs was seen with age, sex, or race. Although anatomic features of meibomianitis were associated with the presence of symptoms (P = .01), 76% (67/88) of the individuals with these anatomic features were asymptomatic; 10.5% (260/2,480) reported that they currently use artificial tears or lubricants. Symptoms and signs of dry eye are common among the elderly but were not associated with age, race, or sex in this population-based sample of elderly Americans. Extrapolating to the United States population aged 65 to 84 years, the study yields an estimate of 4.3 million who experience symptoms of ocular irritation often or all the time.
              Article 0 comments Cited 139 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Contributors
                : Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2012
                Publication date (Electronic): 16 March 2012
                Volume: 7
                Issue: 3
                Electronic Location Identifier: e33688
                Affiliations
                [1 ]State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
                [2 ]Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China
                [3 ]Department of Ophthalmology, People's Hospital of Leshan, Leshan, China
                University of Florida, United States of America
                Author notes

                Conceived and designed the experiments: CL YS SL ZW. Performed the experiments: CL YS SL PW NL JT YH CX. Analyzed the data: CL YS SL ZW. Contributed reagents/materials/analysis tools: CL YS SL PW NL JT YH CX. Wrote the paper: CL YS SL ZW.

                Article
                Publisher ID: PONE-D-11-23216
                DOI: 10.1371/journal.pone.0033688
                PMC ID: 3306287
                PubMed ID: 22438984
                SO-VID: b47f3055-97fa-419e-945c-7b44ac43add4
                Copyright © Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                Date received : 21 November 2011
                Date accepted : 19 February 2012
                Page count
                Pages: 9
                Categories
                Subject: Research Article
                Subject: Biology
                Subject: Anatomy and Physiology
                Subject: Ocular System
                Subject: Model Organisms
                Subject: Toxicology
                Subject: Chemistry
                Subject: Medicinal Chemistry
                Subject: Medicine
                Subject: Anatomy and Physiology
                Subject: Ocular System
                Subject: Ophthalmology
                Subject: Toxicology

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

                Comments

                Comment on this article

                scite_

                Similar content82

                See all similar

                Cited by23

                See all cited by

                Most referenced authors339

                See all reference authors