Kyoto University · Medicine
Professor Hanako Ohashi Ikeda's research lab focuses on retinal degenerative diseases, particularly retinitis pigmentosa, glaucoma, and Bietti's crystalline dystrophy, with an emphasis on understanding disease mechanisms and developing neuroprotective strategies. The lab utilizes stem cell-derived models, including iPSC-derived retinal organoids and retinal pigment epithelium cells, to study disease pathology and screen therapeutic compounds. A central theme is the role of cellular energy metabolism—especially ATP homeostasis—in retinal neuron survival, leading to the discovery and development of small molecules and metabolic modulators (e.g., BCAAs, VCP inhibitors) that protect photoreceptors and RPE cells.
Figures are computed from collected data and may differ slightly.
We report directed differentiaion of retinal precursors in vitro from mouse ES cells. Six3+ rostral brain progenitors are generated by culturing ES cells under serum-free suspension conditions (SFEB culture) in the presence of Wnt and Nodal antagonists (Dkk1 and LeftyA), and subsequently steered to differentiate into Rx+ cells (16%) by treatment with activin and serum. Consistent with the characteristics of early neural retinal precursors, the induced Rx+ cells coexpress Pax6 and the mitotic mar
Trabeculotomy for developmental glaucoma is effective over a long time. There is a fairly good prognosis for visual function of eyes with developmental glaucoma with early detection of the onset, proper treatment, and proper management after trabeculotomy.
Bietti's crystalline dystrophy (BCD) is an intractable and progressive chorioretinal degenerative disease caused by mutations in the <i>CYP4V2</i> gene, resulting in blindness in most patients. Although we and others have shown that retinal pigment epithelium (RPE) cells are primarily impaired in patients with BCD, the underlying mechanisms of RPE cell damage are still unclear because we lack access to appropriate disease models and to lesion-affected cells from patients with BCD. Here, we gener
Neuroprotection may prevent or forestall the progression of incurable eye diseases, such as retinitis pigmentosa, one of the major causes of adult blindness. Decreased cellular ATP levels may contribute to the pathology of this eye disease and other neurodegenerative diseases. Here we describe small compounds (Kyoto University Substances, KUSs) that were developed to inhibit the ATPase activity of VCP (valosin-containing protein), the most abundant soluble ATPase in the cell. Surprisingly, KUSs
In the current study, SD-OCT provided the pattern of photoreceptor degeneration in RP rabbits and the longitudinal changes in each retinal layer through the evaluation of identical areas over time. The time-dependent changes in the retinal structure of RP rabbits showed regional and time-stage variations. In vivo imaging of RP rabbit retinas by using SD-OCT is a powerful method for characterizing disease dynamics and for assessing the therapeutic effects of experimental interventions.
Retinal neuronal cell death underlies many incurable eye diseases such as retinitis pigmentosa (RP) and glaucoma, and causes adult blindness. We have shown that maintenance of ATP levels via inhibiting ATP consumption is a promising strategy for preventing neuronal cell death. Here, we show that branched chain amino acids (BCAAs) are able to increase ATP production by enhancing glycolysis. In cell culture, supplementation of the culture media with BCAAs, but not glucose alone, enhanced cellular
Glaucoma is a major cause of adult blindness due to gradual death of retinal ganglion cells. Currently, no therapeutics are available for the protection of these cells from the cell death. We have recently succeeded in synthesizing novel compounds, KUSs (Kyoto University Substances), which can reduce cellular ATP consumption by specifically inhibiting the ATPase activities of VCP, a major ATPase in the cell, and we have shown that KUSs could mitigate the disease progression of rd10, a mouse mode
It is difficult to identify a target in the peripheral visual field when it is flanked by distractors. In the present study, we investigated this "crowding" effect for biological motion stimuli. Three walking biological motion stimuli were presented horizontally in the periphery with various distances between them, and observers reported the walking direction of the central figure. When the inter-walker distance was small, discriminating the direction became difficult. Moreover, the reported dir
Kyoto University Substance (KUS) 121, an ATPase inhibitor of valosin-containing protein, is a novel neuroprotectant. We tested the safety and effectiveness of KUS121 in patients with acute central retinal artery occlusion (CRAO). We conducted an investigator-initiated, first-in-humans, phase 1/2 clinical trial. Nine patients with non-arteritic CRAO symptoms lasting for 4-48 h were enrolled. These patients received daily intravitreal injections of KUS121 for 3 days: 25 μg (low-dose) in the first
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