Ocular angiogenesis antagonist may yield new therapy

NEW YORK (Reuters Health) – Investigators from the Scripps Research Institute in La Jolla, California have identified a protein fragment that blocks ocular angiogenesis. The fragment could represent a novel treatment for neovascular eye diseases.

In two studies reported in the January 8th issue of the Proceedings of the National Academy of Sciences, Dr. Paul Schimmel and colleagues evaluated the angiogenic properties of a tRNA synthetase fragment in several models of ocular angiogenesis.

Previous study findings have suggested that tryptophanyl-tRNA synthetase (TrpRS) is involved in angiogenesis. In the current studies, the researchers tested the angiogenic properties of two similar TrpRS fragments.

In one study, a naturally occurring TrpRS fragment was tested. This fragment, known as mini TrpRS, results from alternative splicing of the full-length protein and its production is stimulated by interferon-gamma. In the current study, the fragment demonstrated angiostatic activity in a mammalian cell culture system, the chicken embryo, and in two angiogenesis assays in the mouse. In contrast, the full-length protein was inactive.

In the other study, a recombinant COOH-terminal fragment of TrpRS was tested. The recombinant fragment was similar in size to the naturally occurring TrpRS fragment. The investigators found that the fragment inhibited experimentally induced and naturally occurring retinal angiogenesis in murine models. The angiostatic activity was dose-dependent in both models.

While it is difficult to compare potency, no other agents appear to inhibit angiogenesis as strongly as the TrpRS fragments, the researchers note. Another advantage of the TrpRS fragments in terms of treatment potential is that they are naturally occurring and not likely to be immunogenic, the researchers note. Because patients with neovascular eye diseases often have systemic ischemic conditions, local treatment deliver would be ideal.

Proc Natl Acad Sci 2002;99:173-183.

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