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K.U. Loeffler, G. Zahn, A. Vogel, M. Wills, F.G. Holz; Morphologic and Immunohistochemical Evaluation of Laser–Induced CNV–Lesions in Cynomolgus Monkeys After Treatment With Small Molecule Integrin Inhibitor . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5052.
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© ARVO (1962-2015); The Authors (2016-present)
Recent studies have shown marked antiangiogenic effects of integrin α5ß1 inhibitors (antibody fragment F200: ARVO 2003, #580; small molecule JSM6427: ARVO 2005, #4169). We investigated the morphological and immunohistochemical characteristics in eyes with laser–induced choroidal neovascularization (CNV) in Cynomolgus monkeys that were treated with an integrin α5ß1–inhibiting small molecule.
12 eyes of 6 Cynomolgus monkeys were examined by light microscopy and immunohistochemistry (IH) after laser–induced CNV. 3 out of the 6 monkeys had been treated with an integrin α5ß1–inhibiting small molecule (JSM6427) on day 1 and days 8, 15, and 22 after the injury in both eyes while the remaining 3 monkeys were treated with vehicle only and served as "untreated" controls. All eyes were enucleated 4 weeks after the initial insult and processed for histology. Step sections were cut and stained with H&E to identify the respective laser–induced chorioretinal scars. IH was performed using antibodies (Abs) to Factor VIII and CK 18 and a polyclonal Ab to integrin α5ß1. The reaction product was visualized using AEC.
In all eyes, there was labeling with anti–integrin α5ß1 not only of occasional choroidal and retinal vessels and some individual cells within the choroid but particularly of the RPE. This labeling was much less pronounced at the site of the laser lesion, possibly with a wider non–immunoreactive area in eyes treated with JSM6427. Anti–Factor VIII labeled all vessels and in addition some individual cells in chorioretinal lesions in the vehicle–treated eyes.
The results indicate that an inhibitory effect of integrin α5ß1–inhibiting small molecule on laser–induced CNV may be mediated both via a direct effect on newly formed vessels and an interaction with the RPE. In CNV associated with AMD integrin α5ß1 is assumed to play a similarly important role, thus making this molecule a promising target for the treatment of such patients.
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