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Impressum
Recent pharmacological approaches to inhibit lens epithelial cell proliferation, migration and adhesion in vitro
Rieck P., Kojetinsky C., Kriegsch J.
Dept. of Ophthalmology, Charité Medical Faculty, Campus Virchow Hospital, Humbolt Universität Berlin, Augustenburger Platz 1, Berlin
Objective: Beside modification of IOL designs, specific pharmacological
therapy remains a promising approach to reduce posterior capsule opacification.
However, agents which reduce proliferation of LEC are mostly non-selective
and include the potential risk of toxicity towards other intraocular tissues.
We investigated the effect of several selective or nontoxic drugs on LEC
proliferation, migration and adhesion in vitro in different cell culture
models.
Methods: Bovine (BLEC) and human lens epithelial cells (HLEC) were
cultures according to established protocols. The mitotoxin FGF-SAP (0.01-
10 nM) (equimolar conjugation of the growth factor FGF and the toxin saporin)
was tested for its inhibtion of cell proliferation. The naphthylurea suramin
(0.1 - 5 mM) was chosen for inhibition of LEC migration. The potential
of a cyclic RGD-peptide to inhibit LEC adhesion was also investigated.
According to the different experimental approaches, cell counting, thymidine
incorporation, immunohistochemical studies, migration and adhesion assays
were perfomed.
Results: In proliferating cultures that were incubated with 10
nM FGFSAP, 98% of the cells were lysed at Day 4. There was no toxic effect
of FGF-SAP at any dose when the mitotoxin was incubated with cells that
had reached confluency. A dose-dependent significant effect of suramin
on the inhibition of HLEC migration was found even after short (1h) incubation
times. Higher doses (>3 mM) revealed toxic effects. The cyclic RGDpeptide
prevented the adhesion of HLEC on culture dishes and anterior lens capsules.
No toxic side effects of this substance could be observed.
Conclusion: Our results demonstrate the efficiency of three specific
drugs to inhibit proliferation, migration and adhesion in vitro. However,
a combination of these agents may be necessary to block the different
steps of PCO development in vivo. Further investigations have to assess
the inocuity of these interesting substances prior to clinical trials.