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Yiping Jin, Sunil Chauhan, Hyun Soo Lee, Yihe Chen, Charles N. Serhan, Reza Dana; Resolvin D1 Stable Analog Promotes Corneal Allograft Survival. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2375. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Resolvin D1 (RvD1) displays dual anti-inflammatory and pro-resolution activities, as well as anti-angiogenesis actions. Here, we investigated the inhibitory actions of RvD1 on corneal graft rejection.
After corneal grafts from C57BL/6 (H-2b) mice were transplanted onto BALB/c (H-2d) recipient mice, we intravenously injected 100ng/100µl RvD1 analog (RvD1a) or vehicle (0.01% ethanol) to recipient mice on day 0 and once a week afterward. Graft survival was evaluated by slit-lamp biomicroscopy weekly up to 8 weeks. Frequencies of IFN-γ expressing T cells in the host draining lymph nodes (LN) were analyzed using the ELISPOT assay at day 18 post transplantation. Whole-mount grafted corneas were double-stained with anti-CD31 and anti-LYVE-1 antibodies. The areas covered by CD31high/LYVE-1low vessels (blood vessels) or CD31lowLYVE-1high vessels (lymphatic vessels) were measured morphometrically with Image J software.
In the RvD1a-treated group, the frequencies of allosensitized T cells in the host draining LN were significantly decreased in both direct (746+21 vs. 988+54 spots/106 T cells, p=0.014) and indirect (24+4 vs. 43+6 spots/106 T cells, p=0.048) pathways, compared to the vehicle group. RvD1a-treatment also significantly reduced the growth of both blood vessels (7.4+0.6% vs. 12.9+1.3%, p=0.017) and lymphatic vessels (6.2+0.7% vs. 10.8+0.78%, p=0.025) in recipient corneas compared to the vehicle group. There was a significant increase in graft survival in the RvD1a-treated group comparing to the vehicle group by week 8 (82% vs. 45%, p=0.05).
These results suggest that RvD1a-treatment effectively enhances graft survival by decreasing both direct and indirect allosensitization, as well as inhibiting both hemangiogenesis and lymphangiogenesis.
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