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K. G. Sheets, Y. Zhou, J. R. Elison, P. Gjorstrup, W. C. Gordon, D. R. Bergsma, N. G. Bazan; An Analog of Resolvin E1 Inhibits Endothelial Cell Growth in Retina Following Laser-induced Choroidal Neovascularization (CNV). Invest. Ophthalmol. Vis. Sci. 2009;50(13):2967.
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© ARVO (1962-2015); The Authors (2016-present)
We have shown by angiography that fluorescein leakage clouds resulting from initiation of CNV are reduced in the presence of a resolvin E1 analog Rx-10008 (ARVO 2008). Here we show that Rx-10008 inhibits the ramification of endothelial cells within the laser lesion site.
Rx-10008 administration began on the day of laser coagulation, and was compared to ethanol controls. RvE1 analog was given i.p. once a day at 0, +1, +3, +5, and +7 days after burn. Ethanol controls followed this protocol. 143.0 µg/k bw of Rx-10008 was added to saline to total 200 µl at each injection. The original compound was in ethanol (1:1), so ethanol was added for controls. Retinas were collected after 2 weeks following post-lesions, and choroidal flatmounts produced. Immunolocalization was performed with nuclear, cytoskeleton, and endothelial cell markers, and optical slices were recorded throughout the depth of each lesion by confocal microscopy. Endothelial cell pixels were collected at each depth for each lesion in all retinas and summed to produce representative endothelial cell volume.
Depth measurements from the surface of the choroidal flatmount inward toward the sclera revealed that, in both control mice and RvE1 analog treated mice, the maximum amount of endothelial cell labeling occurred at a depth of about 3 µm. Most endothelial cell labeling was reduced to its smallest amount at a depth of 9-22 µm in the control eyes, but only at about 4.4 µm in analog-treated animals. When all endothelial cell labeling was summed for each lesion and the data for all control and treated lesions averaged, lesions from the Rx-10008-treated mice contained half the amount of endothelial cell labeling that control mice exhibited.
Treatment of mice with the Rx-10008 analog following laser-induced CNV greatly reduced (by 50%) the amount of endothelial cells within the lesion site after 2 weeks. Also, the depth of endothelial cell ramification was reduced, suggesting that resolvin and resolvin-like compounds may serve possible therapeutic purposes in AMD.
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