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Veterinary ophthalmology2004; 7(6); 397-405; doi: 10.1111/j.1463-5224.2004.04052.x

Profiles of matrix metalloproteinase activity in equine tear fluid during corneal healing in 10 horses with ulcerative keratitis.

Abstract: Levels of tear film matrix metalloproteinases (MMPs) activity are significantly elevated in horses with ulcerative keratitis and contribute to the excessive breakdown of stromal collagen. Changes in the amount of proteolytic activity in horse tear film during corneal healing and stromal remodeling have not yet been reported, but we hypothesize they should decrease. In the present study we analyzed serial tear fluid from horses with ulcerative keratitis to identify any changes in MMP activity during corneal healing and stromal remodeling. Methods: Samples of tear fluid were obtained from both eyes of 10 horses with ulcerative keratitis on the day of admission (day 1) at the hospital and then at various time points until complete healing of the cornea. Tear film MMP2 and MMP9 activity was determined by quantitative gelatin zymography. In all cases medical treatment included topical applications of equine serum, antibiotics, atropine and systemic administration of anti-inflammatory drugs. Surgical procedures were performed in several cases on day 2 in addition to the medical treatment. Results: The mean total MMP activity (+/- SD) measured in relative standard units (RSU) in the tear fluid of the ulcerated eye (2.44 +/- 1.44) of the 10 horses was significantly higher than the mean in the contralateral eye (0.81 +/- 0.68) (P = 0.006), on the day of admission at the VMTH. The mean MMP activity in these ulcerated eyes significantly decreased (-82.4%) between the first day of admission and the day when the ulcer had completely healed (P = 0.0002). The activity level in the healed eye (0.43 +/- 0.17) was not significantly different to the one in the contralateral eye (0.36 +/- 0.18) on the day of complete corneal healing (P = 0.374). The level of MMP activity in the contralateral eye also decreased from 0.81 +/- 0.68-0.36 +/- 0.18 but this decrease (56%) was not significant (P = 0.069). Conclusions: Ulcerative keratitis in horses is associated with initially high levels of tear film proteolytic activity that decrease as the ulcers heal. The success of medical and surgical treatment of the corneal ulcers is reflected by the enzyme activity in tears. In horses successful treatment does lead to a rapid reduction in tear film proteolytic activity that corresponded with the improvement in the clinical signs of corneal ulceration. Measurement of MMP activity in the tear film might represent a way to monitor the progression of corneal healing in horses with ulcerative keratitis.
Publication Date: 2004-10-30 PubMed ID: 15511281DOI: 10.1111/j.1463-5224.2004.04052.xGoogle Scholar: Lookup
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  • Journal Article

Summary

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The research article explores the fluctuating levels of matrix metalloproteinases (MMPs), enzymes involved in breaking down tissues, in the tears of horses with corneal ulcers. The study found an initial high level of MMPs, which significantly dropped as the ulcers healed, indicating the potential use of MMP levels as a method to monitor the healing process.

Research Objectives and Methodology

  • The primary objective of this research work was to study the levels of matrix metalloproteinases (MMPs) in the tear fluids of horses diagnosed with ulcerative keratitis and understand their role in the process of corneal healing and stromal remodeling.
  • Researchers gathered tear fluid samples from both eyes of ten horses with ulcerative keratitis on the day they were admitted to the hospital, as well as at various intervals until the full healing of the cornea.
  • The activity of two specific MMPs (MMP2 and MMP9) was measured using a method called quantitative gelatin zymography.
  • Horses in the study received medical treatment consisting of topical applications of equine serum, antibiotics, atropine, and systemic anti-inflammatory drugs. Additionally, surgical procedures were conducted on some horses alongside the medical treatment.

Results and Findings

  • The findings revealed a significant initial high level of MMP activity in the tear fluids of the diseased eye compared to the healthy eye. This level significantly diminished as the corneal ulcers healed. Specifically, MMP activity in these ulcerated eyes decreased by 82.4% between the first day of admission and the day when the ulcer was fully healed.
  • Further, once the cornea was entirely healed, the level of MMP activity was not significantly different from that found in the healthy eye. This indicates the successful treatment of corneal ulcers, as reflected by reduced enzyme activity in the tears.
  • Interestingly, the study also documented a decrease in MMP activity in the contralateral (or healthy) eye, but this change was not found to be statistically significant.

Conclusions and Implications

  • The study concluded that high levels of enzymatic activity in the tear film during the initial stages of corneal ulcers in horses decrease significantly as the ulcers heal. Hence, successful medical or surgical treatment is critical in reducing tear film proteolytic activity, which reflects the improvement in the clinical signs of corneal ulceration.
  • The research suggests that measuring MMP activity in tear film might be a practical method to monitor the progression of corneal healing in horses suffering from ulcerative keratitis. This approach can provide potential insights into refining treatment strategies and diagnosing the stage of healing.

Cite This Article

APA
Ollivier FJ, Brooks DE, Van Setten GB, Schultz GS, Gelatt KN, Stevens GR, Blalock TD, Andrew SE, Komaromy AM, Lassaline ME, Kallberg ME, Cutler TJ. (2004). Profiles of matrix metalloproteinase activity in equine tear fluid during corneal healing in 10 horses with ulcerative keratitis. Vet Ophthalmol, 7(6), 397-405. https://doi.org/10.1111/j.1463-5224.2004.04052.x

Publication

ISSN: 1463-5216
NlmUniqueID: 100887377
Country: England
Language: English
Volume: 7
Issue: 6
Pages: 397-405

Researcher Affiliations

Ollivier, F J
  • Department of Large and Small Animal Clinical Sciences, College of Veterinary Medicine, Stockholm, Sweden. ollivier@mail.vetmed.ufl.edu
Brooks, D E
    Van Setten, G B
      Schultz, G S
        Gelatt, K N
          Stevens, G R
            Blalock, T D
              Andrew, S E
                Komaromy, A M
                  Lassaline, M E
                    Kallberg, M E
                      Cutler, T J

                        MeSH Terms

                        • Animals
                        • Corneal Diseases / enzymology
                        • Corneal Diseases / pathology
                        • Corneal Diseases / veterinary
                        • Corneal Ulcer / enzymology
                        • Corneal Ulcer / pathology
                        • Corneal Ulcer / surgery
                        • Corneal Ulcer / veterinary
                        • Female
                        • Horse Diseases / enzymology
                        • Horse Diseases / pathology
                        • Horse Diseases / surgery
                        • Horses
                        • Male
                        • Matrix Metalloproteinase 2 / metabolism
                        • Matrix Metalloproteinase 9 / metabolism
                        • Matrix Metalloproteinases / metabolism
                        • Tears / enzymology
                        • Wound Healing