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Dynamic ocular surface and lacrimal gland changes induced in experimental murine dry eye.

Xiao B, Wang Y, Reinach PS, Ren Y, Li J, Hua S, Lu H, Chen W - PLoS ONE (2015)

Bottom Line: To determine if there is a correlation between severity effects in these models and underlying pathophysiological responses, we compared the time dependent changes in each of these parameters that occur during a 6 week period.Interleukin-17(IL-17), IL-23, IL-6, IL-1, TNF-α, IFN-γ and TGF-β2 levels were estimated by real-time PCR measurements of conjunctival and lacrimal gland samples (LGs).Subsequently, the disease process stabilized for the next four weeks.

View Article: PubMed Central - PubMed

Affiliation: School of Ophthalmology and Optometry, Wenzhou Medical University, Zhejiang, China.

ABSTRACT
Dry eye disease can be a consequence of lacrimal gland insufficiency in Sjögren's Syndrome or increased tear film evaporation despite normal lacrimal gland function. To determine if there is a correlation between severity effects in these models and underlying pathophysiological responses, we compared the time dependent changes in each of these parameters that occur during a 6 week period. Dry eye was induced in 6-week-old female C57BL/6 mice by exposing them to an Intelligently Controlled Environmental System (ICES). Sixty mice were housed in ICES for 1, 2, 4 and 6 weeks respectively. Twelve were raised in normal environment and received subcutaneous injections of scopolamine hydrobromide (SCOP) 3 times daily for 5 days. Another sixty mice were housed in a normal environment and received no treatment. Corneal fluorescein staining along with corneal MMP-9 and caspase-3 level measurements were performed in parallel with the TUNEL assay. Interleukin-17(IL-17), IL-23, IL-6, IL-1, TNF-α, IFN-γ and TGF-β2 levels were estimated by real-time PCR measurements of conjunctival and lacrimal gland samples (LGs). Immunohistochemistry of excised LGs along with flow cytometry in cervical lymph nodes evaluated immune cell infiltration. Light and transmission electron microscopy studies evaluated LGs cytoarchitectural changes. ICES induced corneal epithelial destruction and apoptosis peaked at 2 weeks and kept stable in the following 4 weeks. In the ICES group, lacrimal gland proinflammatory cytokine level increases were much lower than those in the SCOP group. In accord with the lower proinflammatory cytokine levels, in the ICES group, lacrimal gland cytosolic vesicular density and size exceeded that in the SCOP group. ICES and SCOP induced murine dry eye effects became progressively more severe over a two week period. Subsequently, the disease process stabilized for the next four weeks. ICES induced local effects in the ocular surface, but failed to elicit lacrimal gland inflammation and cytoarchitectural changes, which accounts for less dry eye severity in the ICES model than that in the SCOP model.

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ICES Induced Corneal Epithelial Destruction.Corneal epithelial damage assessment by standard corneal fluorescein staining scores in ICES groups (E), the scopolamine-treated group (SCOP) and normal control group (N). *P < 0.05 versus the normal group (N).
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pone.0115333.g001: ICES Induced Corneal Epithelial Destruction.Corneal epithelial damage assessment by standard corneal fluorescein staining scores in ICES groups (E), the scopolamine-treated group (SCOP) and normal control group (N). *P < 0.05 versus the normal group (N).

Mentions: Fluorescein staining assessed changes in corneal epithelial integrity. In the ICES group, after 1 week there was a slight increase in the staining score which peaked at 2 weeks (P< 0.001) and was invariant for the next 4 weeks (Fig. 1). To evaluate if losses in the ICES group of tight junctional barrier function and epithelial integrity were accompanied by increases in MMP-9 expression, its staining pattern was also evaluated. In parallel with the development of corneal fluorescein staining, MMP-9 became the most intense after 2 weeks of ICES, which was unchanged during the following 4 and 6 weeks (Fig. 2). We also compared if there were differences in the development of MMP-9 expression in the ICES and SCOP groups. In the SCOP group, the MMP-9 expression was greater at all times than in the ICES group.


Dynamic ocular surface and lacrimal gland changes induced in experimental murine dry eye.

Xiao B, Wang Y, Reinach PS, Ren Y, Li J, Hua S, Lu H, Chen W - PLoS ONE (2015)

ICES Induced Corneal Epithelial Destruction.Corneal epithelial damage assessment by standard corneal fluorescein staining scores in ICES groups (E), the scopolamine-treated group (SCOP) and normal control group (N). *P < 0.05 versus the normal group (N).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4295848&req=5

pone.0115333.g001: ICES Induced Corneal Epithelial Destruction.Corneal epithelial damage assessment by standard corneal fluorescein staining scores in ICES groups (E), the scopolamine-treated group (SCOP) and normal control group (N). *P < 0.05 versus the normal group (N).
Mentions: Fluorescein staining assessed changes in corneal epithelial integrity. In the ICES group, after 1 week there was a slight increase in the staining score which peaked at 2 weeks (P< 0.001) and was invariant for the next 4 weeks (Fig. 1). To evaluate if losses in the ICES group of tight junctional barrier function and epithelial integrity were accompanied by increases in MMP-9 expression, its staining pattern was also evaluated. In parallel with the development of corneal fluorescein staining, MMP-9 became the most intense after 2 weeks of ICES, which was unchanged during the following 4 and 6 weeks (Fig. 2). We also compared if there were differences in the development of MMP-9 expression in the ICES and SCOP groups. In the SCOP group, the MMP-9 expression was greater at all times than in the ICES group.

Bottom Line: To determine if there is a correlation between severity effects in these models and underlying pathophysiological responses, we compared the time dependent changes in each of these parameters that occur during a 6 week period.Interleukin-17(IL-17), IL-23, IL-6, IL-1, TNF-α, IFN-γ and TGF-β2 levels were estimated by real-time PCR measurements of conjunctival and lacrimal gland samples (LGs).Subsequently, the disease process stabilized for the next four weeks.

View Article: PubMed Central - PubMed

Affiliation: School of Ophthalmology and Optometry, Wenzhou Medical University, Zhejiang, China.

ABSTRACT
Dry eye disease can be a consequence of lacrimal gland insufficiency in Sjögren's Syndrome or increased tear film evaporation despite normal lacrimal gland function. To determine if there is a correlation between severity effects in these models and underlying pathophysiological responses, we compared the time dependent changes in each of these parameters that occur during a 6 week period. Dry eye was induced in 6-week-old female C57BL/6 mice by exposing them to an Intelligently Controlled Environmental System (ICES). Sixty mice were housed in ICES for 1, 2, 4 and 6 weeks respectively. Twelve were raised in normal environment and received subcutaneous injections of scopolamine hydrobromide (SCOP) 3 times daily for 5 days. Another sixty mice were housed in a normal environment and received no treatment. Corneal fluorescein staining along with corneal MMP-9 and caspase-3 level measurements were performed in parallel with the TUNEL assay. Interleukin-17(IL-17), IL-23, IL-6, IL-1, TNF-α, IFN-γ and TGF-β2 levels were estimated by real-time PCR measurements of conjunctival and lacrimal gland samples (LGs). Immunohistochemistry of excised LGs along with flow cytometry in cervical lymph nodes evaluated immune cell infiltration. Light and transmission electron microscopy studies evaluated LGs cytoarchitectural changes. ICES induced corneal epithelial destruction and apoptosis peaked at 2 weeks and kept stable in the following 4 weeks. In the ICES group, lacrimal gland proinflammatory cytokine level increases were much lower than those in the SCOP group. In accord with the lower proinflammatory cytokine levels, in the ICES group, lacrimal gland cytosolic vesicular density and size exceeded that in the SCOP group. ICES and SCOP induced murine dry eye effects became progressively more severe over a two week period. Subsequently, the disease process stabilized for the next four weeks. ICES induced local effects in the ocular surface, but failed to elicit lacrimal gland inflammation and cytoarchitectural changes, which accounts for less dry eye severity in the ICES model than that in the SCOP model.

Show MeSH
Related in: MedlinePlus