KUS-121

Nonarteritic central retinal artery occlusion (NA-CRAO) is a variant of acute ischemic stroke (AIS) and is a cause of sudden severe loss of vision. There are guidelines by the American Heart Association and the American Stroke Association for the care of CRAO patients. This review explores the basis of retinal neuroprotection for CRAO and its potential for improving the outcome of NA-CRAO. Recently, there have been significant advances in research into the use of neuroprotection to treat retinal diseases, including retinal detachment, age-related macular degeneration, and inherited retinal diseases. Also, neuroprotective research in AIS has been extensive, and newer drugs tested, including Uric acid, Nerinetide, and Otaplimastat, with promising results. Progress in cerebral neuroprotection after AIS offers hope for retinal neuroprotection after CRAO; and a possibility of extrapolating research findings from AIS into CRAO. Combining neuroprotection and thrombolysis can extend the therapeutic window for NA-CRAO treatment and potentially improve outcomes. Experimented neuroprotection for CRAO includes Angiopoietin (Comp Ang1), KUS 121, Gene therapy (XIAP), and hypothermia. Efforts in the field of neuroprotection for NA-CRAO should focus on better imaging to delineate the penumbra after an acute episode of NA-CRAO (using a combination of high-definition optical coherence angiography and electrophysiology). Also, research should explore details of pathophysiologic mechanisms involved in NA-CRAO, allowing for further neuroprotective intervention, and closing the gap between preclinical and clinical neuroprotection.

Novel findings of this study are as follows: 1) Kyoto University substance 121 (KUS121), a novel valosin-containing protein (VCP) modulator, can reduce ATP consumption of VCP; 2) KUS121 reduced endoplasmic reticulum (ER) stress and improved cell viability in proximal tubular cells; 3) KUS121 exerted renoprotective effects against ischemia-reperfusion injury; and 4) KUS121 may prevent ischemic acute kidney injury with ATP retention and restoring ER-associated degradation capacity.