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Desiccating stress stimulates expression of matrix metalloproteinases by the corneal epithelium.
Invest Ophthalmol Vis Sci. 2006 Aug; 47(8):3293-302.IO

Abstract

PURPOSE

To determine the effects of experimental dryness on production of matrix metalloproteinases (MMPs) and their physiological inhibitors (TIMPs) by the corneal epithelium.

METHODS

Experimental dry eye (EDE) was created in two strains of mice: BALB/c and C57BL/6. Real-time PCR was performed with MMP and TIMP probes, and the results were analyzed by the comparative C(T) method, selecting the relative mRNA levels in untreated control samples as calibrator. Immunofluorescent staining with specific antibodies immunolocalized MMP proteins in situ. MMP enzymatic activity was evaluated in tears and corneal lysates. Corneal permeability to Oregon green dextran (OGD) and sodium fluorescein was measured. Corneal smoothness was evaluated by graded regularity of a ring reflected off the corneal surface.

RESULTS

Desiccating stress significantly increased levels of MMP-1, -3, -9, and -10 transcripts in the corneal epithelium in C57BL/6 mice, but had no effect on levels of MMP transcripts in the corneal epithelium of BALB/c mice. There was no change in levels of TIMP transcripts except for TIMP-4 which significantly increased on day 10 in C57BL/6 mice. The MMP-1, -3, and -9 concentration in tears significantly increased compared with control levels after EDE for 4 and 6 days, respectively, in C57BL/6 and BALB/c. Changes in MMP protein expression detected by immunofluorescent staining were similar to changes in gene transcripts for most MMPs. EDE increased corneal permeability to OGD and fluorescein and corneal surface irregularity.

CONCLUSIONS

Corneal dryness stimulates production of certain MMPs in a strain-dependent fashion and causes the disruption of the corneal barrier, thus increasing permeability and corneal irregularity.

Authors+Show Affiliations

Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16877394

Citation

Corrales, Rosa M., et al. "Desiccating Stress Stimulates Expression of Matrix Metalloproteinases By the Corneal Epithelium." Investigative Ophthalmology & Visual Science, vol. 47, no. 8, 2006, pp. 3293-302.
Corrales RM, Stern ME, De Paiva CS, et al. Desiccating stress stimulates expression of matrix metalloproteinases by the corneal epithelium. Invest Ophthalmol Vis Sci. 2006;47(8):3293-302.
Corrales, R. M., Stern, M. E., De Paiva, C. S., Welch, J., Li, D. Q., & Pflugfelder, S. C. (2006). Desiccating stress stimulates expression of matrix metalloproteinases by the corneal epithelium. Investigative Ophthalmology & Visual Science, 47(8), 3293-302.
Corrales RM, et al. Desiccating Stress Stimulates Expression of Matrix Metalloproteinases By the Corneal Epithelium. Invest Ophthalmol Vis Sci. 2006;47(8):3293-302. PubMed PMID: 16877394.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Desiccating stress stimulates expression of matrix metalloproteinases by the corneal epithelium. AU - Corrales,Rosa M, AU - Stern,Michael E, AU - De Paiva,Cintia S, AU - Welch,Jonathan, AU - Li,De-Quan, AU - Pflugfelder,Stephen C, PY - 2006/8/1/pubmed PY - 2006/9/1/medline PY - 2006/8/1/entrez SP - 3293 EP - 302 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 47 IS - 8 N2 - PURPOSE: To determine the effects of experimental dryness on production of matrix metalloproteinases (MMPs) and their physiological inhibitors (TIMPs) by the corneal epithelium. METHODS: Experimental dry eye (EDE) was created in two strains of mice: BALB/c and C57BL/6. Real-time PCR was performed with MMP and TIMP probes, and the results were analyzed by the comparative C(T) method, selecting the relative mRNA levels in untreated control samples as calibrator. Immunofluorescent staining with specific antibodies immunolocalized MMP proteins in situ. MMP enzymatic activity was evaluated in tears and corneal lysates. Corneal permeability to Oregon green dextran (OGD) and sodium fluorescein was measured. Corneal smoothness was evaluated by graded regularity of a ring reflected off the corneal surface. RESULTS: Desiccating stress significantly increased levels of MMP-1, -3, -9, and -10 transcripts in the corneal epithelium in C57BL/6 mice, but had no effect on levels of MMP transcripts in the corneal epithelium of BALB/c mice. There was no change in levels of TIMP transcripts except for TIMP-4 which significantly increased on day 10 in C57BL/6 mice. The MMP-1, -3, and -9 concentration in tears significantly increased compared with control levels after EDE for 4 and 6 days, respectively, in C57BL/6 and BALB/c. Changes in MMP protein expression detected by immunofluorescent staining were similar to changes in gene transcripts for most MMPs. EDE increased corneal permeability to OGD and fluorescein and corneal surface irregularity. CONCLUSIONS: Corneal dryness stimulates production of certain MMPs in a strain-dependent fashion and causes the disruption of the corneal barrier, thus increasing permeability and corneal irregularity. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/16877394/Desiccating_stress_stimulates_expression_of_matrix_metalloproteinases_by_the_corneal_epithelium_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.05-1382 DB - PRIME DP - Unbound Medicine ER -