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Jiayi Jin, Shaobo Su; The effect of nicotinamide phosphoribosyl transferase inhibitor JSNMPT-029 on corneal neovascularization. Invest. Ophthalmol. Vis. Sci. 2017;58(8):203. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Many diseases, such as heart failure, tumor occurrence，Huntington's disease are associated with aberrant energy metabolism. Nicotinamide phosphoribosyl transferase (NAMPT) is a rate limiting enzyme catalyzing the synthesis of cellular nicotinamide adenine dinucleotide (NAD+), which is required for ATP production. In this study, we examined the effect of JSNMPT-029, an inhibitor of NAMPT, on inflammatory corneal angiogenesis.
Alkali-induced injured corneas of mice were topically applied with JSNMPT-029 twice a day. Eyes were examined with a slit lamp 7 and 14 days after alkali injury. Mice were scarified and the corneas were harvested for total RNA extraction for real time PCR or for histological analysis with 10% neutral formalin fixation. In vitro, the effect of JSNMPT-029 on migration, proliferation and tube formation by human umbilical vein endothelial cells (HUVECs) were examined. The expression of pro/anti-angiogenenic factor in corneas and HUVECs were examined by real time PCR.
Topical application of JSNMPT-029 to the injured corneas attenuated corneal neovascularization (CNV) with down-regulation of the expression of the pro-angiogenic factors VEGF, b-FGF, TGFβ1 and EGF but up-regulation of the expression of the anti-angiogenic factors Tsp-1, Tsp-2 and ADAMTS-1 in the injured corneas. Furthermore, JSNMPT-029 inhibited the expression of pro-angiogenic factors, migration, proliferation and tube formation by human umbilical vein endothelial cells (HUVECs) in vitro.
Topical application of JSNMPT-029 to the injured corneas attenuated CNV by inhibition of the expression of the pro-angiogenic factors but promotion of the expression of the anti-angiogenic factors in the injured corneas. The data suggest that JSNMPT-029 has therapeutic potential for angiogenesis- associated diseases such as CNV.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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