H. Mietz et al., A MOUSE MODEL TO STUDY THE WOUND-HEALING RESPONSE FOLLOWING FILTRATION SURGERY, Graefe's archive for clinical and experimental ophthalmology, 236(6), 1998, pp. 467-475
Background: Failure of trabeculectomy is attributed to an exaggerated
wound healing response at the episcleral level. We have developed a si
mple technique in mice that creates corneoscleral wounds and used it t
o study the role of growth factors in wound healing associated with lo
ss of fistular patency. In addition, the effect of suramin on the woun
d healing response has been investigated. Materials and methods: Using
black C57B1/6 mice, we created a fistula from the subconjunctival spa
ce to the anterior chamber by external penetration with a 25-gauge nee
dle through the bulbur conjunctiva. Eyes were examined by light micros
copy at different times following surgery and evaluated for the presen
ce of growth factors in the sclerosing wound by immunohistochemistry.
In an additional group, suramin (1.0 mg/ml) was applied topically five
times. Results: The limbal/ scleral wounds closed rapidly. Granulatio
n tissue consisting mostly of fibroblasts developed within the first 2
days, and the collagen component increased over time. By 4 weeks, the
wound was completely healed. We found that within 1 day after surgery
GF beta 2 reached high intensity. TGF beta 1 and PDGF A reached maxim
al intensity by day 2 and remained elevated for about a week. PDGF B w
as present at moderate intensity even before surgery. Myofibroblastic
differentiation was observed from days 2 to 7. Suramin-treated wounds
showed a decrease of cells and delay in fibroblast maturation. TGF bet
a 1 and TGF beta 2 levels persisted longer than in the controls, while
PDGF A and PDGF B levels were lower than in the controls at all time
points. Conclusions: The mouse corneoscleral wound model that we have
developed mimics the process of wound healing and fistulizing surgery
that takes place in other animal models and in human eyes in which the
outcome of the surgery is poor. Our analysis of the appearance of gro
wth factors associated with wound healing demonstrates that PDGF A as
well as TGF beta 1 and TGF beta 2 appear early in the process at high
levels and are potential targets for interventive strategies to ensure
channel patency. Suramin has a distinct effect on the wound healing p
rocess and expression of growth factors and may be a promising substan
ce for clinical use.