Study: excess gelatinase B found in patients with conjunctivitis

By controlling or preventing the release of gelatinase B, surgeons believe a new type of allergy treatment may be developed.

ByNicole Nader

RIYADH — An overabundance of gelatinase B found in the conjunctivae of patients with vernal keratoconjunctivitis may be a clue to the pathophysiology of the disease, according to a study here.

“We think this excessive expression of gelatinase B in the eosinophils of the conjunctiva may acutely regulate events and cause an inflammatory response in patients with vernal keratoconjunctivitis (VKC),” said Ahmed M. Abu El-Asrar, MD, PhD, of the department of ophthalmology at King Abdulaziz University Hospital here.

Gelatinase is an extracellular proteolytic enzyme. It is a key enzyme in normal extracellular matrix turnover and can play a role in the extracellular matrix breakdown associated with pathological conditions, according to the study.

In the small study, Dr. Abu El-Asrar found an overproduction of this enzyme in the eosinophils of patients with VKC, compared to patients with a normal conjunctiva and no allergy-related condition.

“It is likely that, in patients with VKC, the eosinophils are triggered to synthesize gelatinase B in overabundance,” he said.

The exact cause of this release is unknown; however, Dr. Abu El-Asrar and colleagues believe this mechanism of action should be investigated for future therapeutic treatments concerning VKC.

The study was published in Archives of Ophthalmology.

Study methods and selection

The study included 12 male patients aged 7 to 17 years with active VKC. Patients’ symptoms included itchiness, redness, tearing and sensitivity to light. According to the study, each patient had the limbal form of the disease, characterized by broad gelatinous infiltrates of the limbus.

During the study, limbal conjunctival biopsy specimens were taken from each patient, and a complete ophthalmic examination noted all corneal and conjunctival changes. Identical samples were taken from a control group of 12 male patients without VKC. A number of tests and analytical elements were used to evaluate the cultures.

“Subjects were studied with immunohistochemical techniques, a monoclonal antibody against gelatinase B and eosinophil peroxidase,” he said.

Additional tests were performed on the specimens of 10 VKC patients and seven control patients using quantitative zymography.

Significant gelatinase B levels

In the control group, gelatinase B was traced in eight of the 12 normal cultures. This activity was located in the polymorphonuclear cells located in the vascular lumens and perivascular area, Dr. Abu El-Asrar said. However, the study found this minimal amount insignificant.

Additionally, gelatinase A — a close relative of gelatinase B with less toxicity to the conjunctiva — was traceable in both the control cultures and the VKC cultures. After statistical analysis, the difference between these groups (P = .08) was insignificant, according to Dr. Abu El-Asrar and colleagues.

Previous studies have shown that gelatinase A has been involved in basal extracellular matrix turnover events. However, gelatinase B has been shown to be involved in more acute activity, and the evidence shows here as well.

“The numbers of gelatinase B-positive cells in the VKC specimens were significantly greater than the numbers found in control specimens,” Dr. Abu El-Asrar said.

Gelatinase B cells were found in the epithelial and stromal inflammatory infiltrate of VKC patients.

In comparison with normal conjunctiva, the VKC conjunctiva had a significant increase of gelatinase B cells, with a statistical difference of P < .02, the study found.

“The up-regulation of gelatinase B in this study is consistent with previous studies that documented the increased expression in subjects with allergic disorders, like asthma,” Dr. Abu El-Asrar added.

Zymography analysis also echoed these results, with an even higher level of gelatinase B found in the VKC cultures. The value was statistically significant at P < .03, when compared with normal cultures.

According to the study, this excess of gelatinase B suggests that this enzyme may be involved in the pathological changes of VKC. A number of factors may trigger the response of overproduction, according to the study.

Possible cause of pathology

“We think that cytokines are involved in the influx of gelatinase B,” Dr. Abu El-Asrar said.

Certain types of cytokines (TH2-derived cytokines interleukin-3, interleukin-5 and granulocyte-macrophages) may stimulate, prolong or even activate eosinophil survival and gelatinase B cells, according to the study.

“There is strong evidence that TH2-type cytokines are centrally involved in the pathogenesis of VKC and other allergic diseases,” Dr. Abu El-Asrar said.

Additionally, researchers speculate another component, CC chemokines, may play a role in the pathogenesis of VKC. CC chemokines are involved in recruiting and activating eosinophils, which harbor gelatinase B, he said.

Further examination is needed to determine why and how these factors inhibit the release of gelatinase B in eosinophils, causing the breakdown of conjunctiva in VKC.

Once the intricacies of this pathology are understood, progression toward a treatment of VKC, directed toward controlling the release of gelatinase B, may provide a cure for the disorder.

For Your Information:

Ahmed M. Abu El-Asrar, MD, PhD, can be reached at the Department of Ophthalmology, King Abdulaziz University Hospital, Airport Rd., P.O. Box 245, Riyadh 11411, Saudi Arabia; e-mail abuasrar@KSU.edu.sa.

Reference:

Abu El-Asrar AM, Van Aelst I, et al. Gelatinase B in vernal keratoconjunctivitis. Arch Ophthalmol. 2001;119:1505-1511.