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Tear film MMP accumulation and corneal disease
V A Smith1, H Rishmawi, H Hussein
1University of Bristol, Division of Ophthalmology, Bristol Eye Hospital, Bristol BS1 2LX, UK. Val.Smith@bristol.ac.uk
Background/Aims:
Matrix metalloproteinases (MMPs) accumulate in the tears of patients with active peripheral ulcerative keratitis (PUK) but it is unknown whether these enzymes have a central role in disease progression. The aims of the present investigation were to determine the source of these enzymes and to ascertain whether their accumulation in tears is a phenomenon specific to PUK or a general feature of other anterior segment diseases.
Methods:
The experimental samples were obtained from the culture media of conjunctival and corneal epithelial cells, from fractionated blood plasma and leucocytes of healthy subjects and patients with rheumatoid arthritis, and from the tears of healthy subjects and patients with a variety of anterior segment diseases. The MMPs of all samples were visualised by zymography and tear samples were assayed using nitrophenol acetate and an MMP-9 susceptible quenched fluorescent peptide as substrate.
Results:
The major MMPs that accumulate in the tears of patients with rheumatoid arthritis with active ocular disease are MMP-9 and a species of M(r) 116,000. By comparing the zymographic activity profiles of the gelatinases present in the samples obtained, it was deduced that the main source of these MMPs was granulocytes. Their accumulation in tears was not unique to patients with PUK; detectable amounts of the enzymes also occurred in the tears of patients with keratoconus with associated atopic disease, patients undergoing treatment for herpetic eye disease, and patients with systemic and non-systemic dry eye disease.
Conclusion:
The MMPs that accumulate in tears are mainly derived from granulocytes. This may be effected by autoimmune diseases that involve ocular tissue or by ocular diseases that induce an inflammatory response.
Insights
Matrix metalloproteinases (MMPs) found in tears originate mainly from granulocytes. Their presence is not exclusive to peripheral ulcerative keratitis (PUK) but occurs in various ocular inflammatory diseases.
Area of Science:
- Ophthalmology
- Immunology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are present in the tears of patients with active peripheral ulcerative keratitis (PUK).
- The specific source and broader relevance of MMP accumulation in ocular surface diseases remain unclear.
Purpose of the Study:
- To identify the cellular source of MMPs accumulating in tears.
- To determine if MMP accumulation is specific to PUK or a common feature of other anterior segment diseases.
Main Methods:
- Collected samples from cultured ocular surface cells, blood components, and tears of healthy individuals and patients with various eye conditions.
- Utilized zymography to visualize MMPs and specific assays to quantify MMP-9 activity in tear samples.
Main Results:
- Matrix metalloproteinase-9 (MMP-9) and a high molecular weight species were the primary MMPs detected in tears of patients with active ocular disease.
- Zymographic analysis indicated granulocytes as the main source of these MMPs.
- Elevated MMP levels were observed not only in PUK but also in keratoconus with atopy, herpetic eye disease, and dry eye conditions.
Conclusions:
- The primary source of MMPs in tears is granulocytes.
- MMP accumulation in tears is associated with autoimmune diseases affecting ocular tissues or other ocular diseases that trigger inflammation.