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Y. Zhou, W. C. Gordon, J. R. Elison, P. Gjorstrup, D. R. Bergsma, N. G. Bazan; Topical Administration of RX-10045 Reduces Laser-induced Choroidal Neovascularization. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2965.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the effectiveness of topical administration of RX-10045 in a mouse CNV model. RX-10045 is the isopropyl ester product of the resolvin analog RX-10008.
RX-10045 (300µg/ml in PBS) was topically applied to both eyes of awake mice at a drop size of 1 µl. The dose was selected based on past successful dosing in a model of murine dry eye (ARVO 2008). Control mice received equal amounts of PBS. Treatments started one hour before laser treatment, and continued 4 times a day at days +1, +3, +5, and +7. Fundus fluorescein angiography of leakage clouds and optical coherence tomography (OCT) was on days 7 and 14 post-laser treatment. Lesion areas were calculated from each OCT scan and volumes estimated from the sum of all OCT scans across each lesion site in both treatment and control mice. The extent of RPE cell ramification above each lesion was also estimated from successive OCT scans across each lesion site for all sites within both treated and control animals. On day 15, eyes were enucleated and choroidal flatmounts prepared for immunolocalizations by confocal microscopy.
There was no difference in leakage cloud size between control and RX-10045 treated eyes by day 7 post-laser treatment. However, by day 14, the number of severe leakage clouds in the RX-10045-treated eyes were diminished by 50% compared to those in control eyes. Analysis of serial OCT lesion scans of the eyes at days 7 and 14 allowed us to estimate volumes of the lesion sites in treated and control eyes, revealing a reduction in volume of about 33% in RX-10045-treated eyes, as compared to controls. Finally, serial OCT scans revealed RPE cells beginning to over-cap the lesion sites. Shrinkage of the opening above each lesion as it was slowly filled with RPE cells was seen; these openings closed faster in RX-10045-treated eyes than in the controls.
Topical treatment with RX-10045 reduced retinal leakage clouds in this murine model of CNV and accelerated healing, consistent with pharmacokinetic properties of RX-10045 on topical eye administration in multiple species. While the effect approached the magnitude previously seen on systemic administration of RX-10008 in this model further dose optimization is planned. The data indicate the potential for topical treatment with resolvins and resolvin analogs for posterior eye diseases.
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