Abstract
Neurodegeneration caused with retinal ischemia or high intraocular pressure is irreversible in general. We have focused on the role of hypoxia-inducible factor (HIF) in retinal homeostasis and revealed that HIF inhibition may be effective against retinal neovascular and neurodegeneration. In this study, we performed in vitro screening of natural products and found halofuginone, which is a derivative of febrifugine extracted from hydrangea, as a novel HIF inhibitor. Administration of halofuginone showed a significant neuroprotective effect by inhibiting HIF-1α expression in a murine retinal ischemia-reperfusion model histologically and functionally. These results indicate that halofuginone can be a neuroprotective agent in ischemic retinal degenerative diseases.
Highlights
Among eye diseases, therapies for retinal neurodegeneration caused by acute ischemia or high intraocular pressure are limited
We examined the neuroprotective effect of halofuginone in a murine model of retinal ischemia-reperfusion (I/R)
Jt.eMnodl.eSdcil.a2t0e1n9,c2ie0,sx(Figure 7D) after I/R injury were significantly (p = 0.047, 0.006) improved6ionf t1h7e halofuginone-treated group. These results suggested that halofuginone had a neuroprotective effect imfupnrcotvioendalilny atghaeinhsatlIo/fRugdianmonage-et.reated group
Summary
Therapies for retinal neurodegeneration caused by acute ischemia or high intraocular pressure are limited. Development of an effective therapeutic approach is needed for such diseases. Hypoxia-inducible factor (HIF) plays an important role in cellular homeostasis especially under hypoxic condition induced by tissue ischemia. In case of the eye, ectopic expression and pathological contribution of HIF is found in acute ischemic [2] and in chronically progressing neurodegenerative glaucomatous retinas [3]. We explore a novel HIF inhibitor to establish a therapeutic approach against inner retinal neurodegeneration while many of known HIF inhibitors such as topotecan and doxorubicin are concerned about systemic side effects [4,5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
