A mouse model of keratoconjunctivitis sicca

Dilek Dursun, Min Wang, Dagoberto Monroy, De Quan Li, Balakrishna L Lokeshwar, Michael E. Stern, Stephen C. Pflugfelder

Research output: Contribution to journalArticle

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Abstract

PURPOSE. To evaluate the effects of pharmacologic inhibition of aqueous tear production and desiccating environmental stress on aqueous tear production, tear clearance, corneal epithelial permeability, and conjunctival epithelial morphology, proliferation, and conjunctival goblet cell differentiation. METHODS. Aqueous tear production was inhibited by applying transdermal scopolamine (scop) patches to the depilated mid-tail of female MC, CBA mice. Desiccating environmental stress was created by placing mice in a hood with a continuous airflow blower. Aqueous tear production and volume, tear clearance, and corneal barrier function were compared in four experimental groups: untreated control mice, mice placed in the blower hood, mice treated with a scop patch, and mice treated with a scop patch and blower hood (scop patch + blower). Cotton threads were used to evaluate aqueous tear production and volume. Tear clearance was assessed by fluorometric measurement of collected tear fluid 15 minutes after instillation of 1% sodium fluorescein. Corneal epithelial barrier function was assessed by fluorometric measurement of carboxyfluorescein uptake. Conjunctival morphology and goblet cell density were evaluated in stained histologic sections. Conjunctival epithelial proliferation was assessed by bromodeoxyuridine (BrdU) labeling. RESULTS. Significant decreases in cotton thread wetting and tear clearance were observed in mice treated with a scop patch (P < 0.001) or with a scop patch and blower desiccation (P < 0.001), with a greater reduction in tear clearance in the latter group. Significantly increased corneal carboxyfluorescein uptake was noted in the scop patch group compared with untreated mice (P = 0.05) and in the scop patch + blower group compared with all the other groups (P < 0.0001). Changes in conjunctival epithelial morphology and a significant decrease in conjunctival goblet cell density (P < 0.001) were observed in the scop patch + blower group compared with the untreated control group. The number of proliferating conjunctival epithelial cells was significantly greater in the scop patch + blower group. CONCLUSIONS. Pharmacologic inhibition of tear production in mice is accompanied by ocular surface epithelial changes resembling acerbated by desiccating environmental stress. Cholinergic stimulated tear production appears to be essential for maintaining a healthy ocular surface.

Original languageEnglish (US)
Pages (from-to)632-638
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume43
Issue number3
StatePublished - Mar 11 2002
Externally publishedYes

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Keratoconjunctivitis Sicca
Tears
Scopolamine Hydrobromide
Goblet Cells
Cell Count
Transdermal Patch
Desiccation
Inbred CBA Mouse
Control Groups
Bromodeoxyuridine
Fluorescein

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Dursun, D., Wang, M., Monroy, D., Li, D. Q., Lokeshwar, B. L., Stern, M. E., & Pflugfelder, S. C. (2002). A mouse model of keratoconjunctivitis sicca. Investigative Ophthalmology and Visual Science, 43(3), 632-638.

A mouse model of keratoconjunctivitis sicca. / Dursun, Dilek; Wang, Min; Monroy, Dagoberto; Li, De Quan; Lokeshwar, Balakrishna L; Stern, Michael E.; Pflugfelder, Stephen C.

In: Investigative Ophthalmology and Visual Science, Vol. 43, No. 3, 11.03.2002, p. 632-638.

Research output: Contribution to journalArticle

Dursun, D, Wang, M, Monroy, D, Li, DQ, Lokeshwar, BL, Stern, ME & Pflugfelder, SC 2002, 'A mouse model of keratoconjunctivitis sicca', Investigative Ophthalmology and Visual Science, vol. 43, no. 3, pp. 632-638.
Dursun D, Wang M, Monroy D, Li DQ, Lokeshwar BL, Stern ME et al. A mouse model of keratoconjunctivitis sicca. Investigative Ophthalmology and Visual Science. 2002 Mar 11;43(3):632-638.
Dursun, Dilek ; Wang, Min ; Monroy, Dagoberto ; Li, De Quan ; Lokeshwar, Balakrishna L ; Stern, Michael E. ; Pflugfelder, Stephen C. / A mouse model of keratoconjunctivitis sicca. In: Investigative Ophthalmology and Visual Science. 2002 ; Vol. 43, No. 3. pp. 632-638.
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abstract = "PURPOSE. To evaluate the effects of pharmacologic inhibition of aqueous tear production and desiccating environmental stress on aqueous tear production, tear clearance, corneal epithelial permeability, and conjunctival epithelial morphology, proliferation, and conjunctival goblet cell differentiation. METHODS. Aqueous tear production was inhibited by applying transdermal scopolamine (scop) patches to the depilated mid-tail of female MC, CBA mice. Desiccating environmental stress was created by placing mice in a hood with a continuous airflow blower. Aqueous tear production and volume, tear clearance, and corneal barrier function were compared in four experimental groups: untreated control mice, mice placed in the blower hood, mice treated with a scop patch, and mice treated with a scop patch and blower hood (scop patch + blower). Cotton threads were used to evaluate aqueous tear production and volume. Tear clearance was assessed by fluorometric measurement of collected tear fluid 15 minutes after instillation of 1{\%} sodium fluorescein. Corneal epithelial barrier function was assessed by fluorometric measurement of carboxyfluorescein uptake. Conjunctival morphology and goblet cell density were evaluated in stained histologic sections. Conjunctival epithelial proliferation was assessed by bromodeoxyuridine (BrdU) labeling. RESULTS. Significant decreases in cotton thread wetting and tear clearance were observed in mice treated with a scop patch (P < 0.001) or with a scop patch and blower desiccation (P < 0.001), with a greater reduction in tear clearance in the latter group. Significantly increased corneal carboxyfluorescein uptake was noted in the scop patch group compared with untreated mice (P = 0.05) and in the scop patch + blower group compared with all the other groups (P < 0.0001). Changes in conjunctival epithelial morphology and a significant decrease in conjunctival goblet cell density (P < 0.001) were observed in the scop patch + blower group compared with the untreated control group. The number of proliferating conjunctival epithelial cells was significantly greater in the scop patch + blower group. CONCLUSIONS. Pharmacologic inhibition of tear production in mice is accompanied by ocular surface epithelial changes resembling acerbated by desiccating environmental stress. Cholinergic stimulated tear production appears to be essential for maintaining a healthy ocular surface.",
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AU - Dursun, Dilek

AU - Wang, Min

AU - Monroy, Dagoberto

AU - Li, De Quan

AU - Lokeshwar, Balakrishna L

AU - Stern, Michael E.

AU - Pflugfelder, Stephen C.

PY - 2002/3/11

Y1 - 2002/3/11

N2 - PURPOSE. To evaluate the effects of pharmacologic inhibition of aqueous tear production and desiccating environmental stress on aqueous tear production, tear clearance, corneal epithelial permeability, and conjunctival epithelial morphology, proliferation, and conjunctival goblet cell differentiation. METHODS. Aqueous tear production was inhibited by applying transdermal scopolamine (scop) patches to the depilated mid-tail of female MC, CBA mice. Desiccating environmental stress was created by placing mice in a hood with a continuous airflow blower. Aqueous tear production and volume, tear clearance, and corneal barrier function were compared in four experimental groups: untreated control mice, mice placed in the blower hood, mice treated with a scop patch, and mice treated with a scop patch and blower hood (scop patch + blower). Cotton threads were used to evaluate aqueous tear production and volume. Tear clearance was assessed by fluorometric measurement of collected tear fluid 15 minutes after instillation of 1% sodium fluorescein. Corneal epithelial barrier function was assessed by fluorometric measurement of carboxyfluorescein uptake. Conjunctival morphology and goblet cell density were evaluated in stained histologic sections. Conjunctival epithelial proliferation was assessed by bromodeoxyuridine (BrdU) labeling. RESULTS. Significant decreases in cotton thread wetting and tear clearance were observed in mice treated with a scop patch (P < 0.001) or with a scop patch and blower desiccation (P < 0.001), with a greater reduction in tear clearance in the latter group. Significantly increased corneal carboxyfluorescein uptake was noted in the scop patch group compared with untreated mice (P = 0.05) and in the scop patch + blower group compared with all the other groups (P < 0.0001). Changes in conjunctival epithelial morphology and a significant decrease in conjunctival goblet cell density (P < 0.001) were observed in the scop patch + blower group compared with the untreated control group. The number of proliferating conjunctival epithelial cells was significantly greater in the scop patch + blower group. CONCLUSIONS. Pharmacologic inhibition of tear production in mice is accompanied by ocular surface epithelial changes resembling acerbated by desiccating environmental stress. Cholinergic stimulated tear production appears to be essential for maintaining a healthy ocular surface.

AB - PURPOSE. To evaluate the effects of pharmacologic inhibition of aqueous tear production and desiccating environmental stress on aqueous tear production, tear clearance, corneal epithelial permeability, and conjunctival epithelial morphology, proliferation, and conjunctival goblet cell differentiation. METHODS. Aqueous tear production was inhibited by applying transdermal scopolamine (scop) patches to the depilated mid-tail of female MC, CBA mice. Desiccating environmental stress was created by placing mice in a hood with a continuous airflow blower. Aqueous tear production and volume, tear clearance, and corneal barrier function were compared in four experimental groups: untreated control mice, mice placed in the blower hood, mice treated with a scop patch, and mice treated with a scop patch and blower hood (scop patch + blower). Cotton threads were used to evaluate aqueous tear production and volume. Tear clearance was assessed by fluorometric measurement of collected tear fluid 15 minutes after instillation of 1% sodium fluorescein. Corneal epithelial barrier function was assessed by fluorometric measurement of carboxyfluorescein uptake. Conjunctival morphology and goblet cell density were evaluated in stained histologic sections. Conjunctival epithelial proliferation was assessed by bromodeoxyuridine (BrdU) labeling. RESULTS. Significant decreases in cotton thread wetting and tear clearance were observed in mice treated with a scop patch (P < 0.001) or with a scop patch and blower desiccation (P < 0.001), with a greater reduction in tear clearance in the latter group. Significantly increased corneal carboxyfluorescein uptake was noted in the scop patch group compared with untreated mice (P = 0.05) and in the scop patch + blower group compared with all the other groups (P < 0.0001). Changes in conjunctival epithelial morphology and a significant decrease in conjunctival goblet cell density (P < 0.001) were observed in the scop patch + blower group compared with the untreated control group. The number of proliferating conjunctival epithelial cells was significantly greater in the scop patch + blower group. CONCLUSIONS. Pharmacologic inhibition of tear production in mice is accompanied by ocular surface epithelial changes resembling acerbated by desiccating environmental stress. Cholinergic stimulated tear production appears to be essential for maintaining a healthy ocular surface.

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