国立研究開発法人 国立成育医療研究センター National Center for Child Health and Development

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Scholar & Enterprise

Scholar & Enterprise

Laboratory for Visual Science

Using a combination of clinical and basic scientific approaches, our laboratory investigates intractable eye diseases that threaten vision. Our goal is to define the pathogenesis and molecular mechanism underlying eye diseases as well as to develop novel diagnostic techniques and therapy using the methodologies of biochemistry, electrophysiology, molecular biology and regenerative cell biology.

In our previous research, we proposed that patients undergo novel surgery for retinopathy of prematurity, which has facilitated good visual outcomes. Histopathological investigation by our laboratory has clarified the origin and differentiation of eye tissues during embryogenesis, and the pathogenesis of a variety of congenital anomalies. Our laboratory has identified numerous gene mutations, including PAX6 and ‘eyes absent’, in a variety of congenital eye anomalies. Functional in vitro and in vivo analysis has clarified the molecular mechanism of eye morphogenesis and determined the visual system.

In a world-first, our laboratory generated self-induced retinal ganglion cells (RGCs) with functional axons from human induced pluripotent stem cells and embryonic stem cells, which facilitate in vitro assays using human disease-specific cells. The ability to generate RGCs with functional axons uniformly and at a high rate may contribute to both basic and clinical science, including embryology, neurology, pathognomy, and will advance medicine and drug development for various optic nerve diseases that threaten vision.

Generation of self-induced retinal ganglion cells with functional axons from human and murine induced pluripotent stem cells and embryonic stem cells

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Leaders

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Bibliography

2019

  1. Hirayama J, Alifu Y, Hamabe R, Yamaguchi S, Tomita J, Maruyama Y, Asaoka Y, Nakahama K, Tamaru T, Takamatsu K, Takamatsu N, Hattori A, Nishina S, Azuma N, Kawahara A, Kume K, Nishina H. The clock components Period2, Cryptochrome1a, and Cryptochrome2a function in establishing light-dependent behavioral rhythms and/or total activity levels in zebrafish. Sci Rep 2019 Jan 17;9(1):196. doi: 10.1038/s41598-018-37879-8
  2. Kurata K, Hosono K, Hayashi T, Mizobuchi K, Katagiri S, Miyamichi D, Nishina S, Sato M, Azuma N, Nakano T, Hotta Y. X-linked Retinitis Pigmentosa in Japan: Clinical and Genetic Findings in Male Patients and Female Carriers. Int J Mol Sci. 2019 Mar 26;20(6):1518. doi: 10.3390/ijms20061518.
  3. Tanaka S, Yokoi T, Azuma N. Foveal neovascularization detected by optical coherence tomography angiography in incontinentia pigmenti. JAMA Ophthalmol. 2019 Mar 1;137(3):e184197. doi: 10.1001/jamaophthalmol.2018.4197.
  4. Tanaka S, Yokoi T, Katagiri S, Yoshida T, Nishina S, Azuma N. Severe recurrent fobrovascular prolifertion after combined intravitreal bevacizmab injection and laser photocoagulation for aggressiove posterior retinopathy of prematurity. Retin Cases Brief Rep. 2019 Jul 17. doi: 10.1097/ICB.0000000000000887. [Epub ahead of print]

2018

  1. Katagiri S, Yokoi T, Yoshida-Uemura T, Nishina S, Azuma N. Characteristics of retinal breaks and surgical outcomes in rhegmatogenous retinal detachment in familial exudative vitreoretinopathy. Ophthalmology Retina, 2018;2(7):720-725 doi: 10.1016/j.oret.2017.11.003.
  2. Hosono K, Nishina S, Yokoi T, Katagiri S, Saitsu H, Kurata K, Miyamichi D, Hikoya A, Mizobuchi K, Nakano T, Minoshima S, Fukami M, Kondo H, Sato M, Hayashi T, Azuma N, Hotta Y. Molecular Diagnosis of 34 Japanese Families with Leber Congenital Amaurosis Using Targeted Next Generation Sequencing. Sci Rep. 2018 May 29;8(1):8279. doi: 10.1038/s41598-018-26524-z.
  3. Takahashi M, Yokoi T, Katagigi S, Yoshida-Uemura T, Nishina, S, Azuma N. Surgical treatments for fibrous tissue extending to the posterior retina in eyes with familial exudative vitreoretinopathy. Jpn J Ophthalmol, 2018; 62(1): 63-67. doi: 10.1007/s10384-017-0547-4.
  4. Yokoi T, Katagiri S, Hiraoka M, Nakayama Y, Hosono K, Hotta Y, Nishina S, Azuma N. Atypical form of retinopathy of prematurity with severe fibrovascular proliferation on the optic disc region. Retina, 2018; 38(8):1605-1612. doi: 10.1097/IAE.0000000000001779.
  5. Yoshida T, Katagiri S, Yokoi T, Nishina S, Azuma N. Optical coherence tomography and video recording of a case of bilateral contractile peripapillary staphyloma. Am J Ophthalmol Case Rep. 2018;13:66-69. doi: 10.1016/j.ajoc.2018.12.002.

2017

  1. Seko Y, Azuma N, Yokoi T, Kami D, Ishii R, Nishina S, Toyoda M, Shimokawa H, Umezawa A. Anteroposterior Patterning of Gene Expression in the Human Infant Sclera: Chondrogenic Potential and Wnt Signaling. Curr Eye Res 2017; 42(1)145-154. doi: 10.3109/02713683.2016.1143015.
  2. Yoshida-Uemura T, Katagiri S, Yokoi T, Nishina S, Azuma N. Different foveal schisis patterns in each retinal layer in eyes with hereditary juvenile retinoschisis evaluated by en-face optical coherence tomography. Graefes Arch Clin Exp Ophthalmol. 2017;255(4):719-723. doi: 10.1007/s00417-016-3552-2.
  3. Katagiri S, Nishina S, Yokoi T, Mikami M, Nakayama Y, Tanaka M, Azuma N. Retinal structure and function in eyes with optic nerve hypoplasia. Sci Rep. 2017 Feb 16;7:42480. doi: 10.1038/srep42480.
  4. Nishina S, Katagiri S, Nakazawa A, Kiyotani C, Yokoi T, Azuma N. Atypical intravitreal growth of retinoblastoma with a multi-branching configuration. Am J Ophthalmol Case Rep. 2017; 7: 4-8. doi: 10.1016/j.ajoc.2017.04.003.
  5. Yokoi T, Tanaka T, Matsuzaka E, Tamalu F, Watanabe S, Nishina S, Azuma N. Effects of neuroactive agents on axonal growth and pathfinding of retinal ganglion cells generated from human stem cells. Sci Rep . 2017 Dec 1;7(1):16757. doi: 10.1038/s41598-017-16727-1.
  6. Ozawa H, Yamane M, Inoue E, Yoshida-Uemura T, Katagiri S, Yokoi T, Nishina S, Azuma N. Long-term surgical outcome of conventional trabeculotomy for childhood glaucoma. Jpn J Ophthalmol, 2017 ;61(3):237-244. doi: 10.1007/s10384-017-0506-0.

2016

  1. Yokoi T, Nakayama Y, Nishina S, Azuma N. The role of vitreoretinal traction in the pathogenesis of maculopathy associated with optic disc pits. Graefes Arch Clin Exp Ophthalmol. 2016 ;254(9):1859-1860. doi: 10.1007/s00417-016-3380-4.
  2. Tanaka T, Yokoi T, Tamalu F, Watanabe S, Nishina S, Azuma N. Generation of retinal ganglion cells with functional axons from mouse embryonic stem cells and induced pluripotent stem cells. Invest Ophthalmol Vis Sci, 2016;57(7):3348-3359. doi: 10.1167/iovs.16-19166.
  3. Nakayama Y, Katagiri S, Yokoi T, Ui M, Nishina S, Azuma N. Successful scleral buckling of late-onset visual decrease in eye with retinal folds. Doc Ophthalmol. 2016; 133(2):145-149. doi: 10.1007/s10633-016-9559-5.
  4. Katagiri S, Yokoi T, Mikami M, Nishina S, Azuma N. Outer retinal deformity detected by optical coherence tomography in eyes with foveal hypoplasia. Graefes Arch Clin Exp Ophthalmol. 2016; 254(11):2197-2201. doi: 10.1007/s00417-016-3385-z.
  5. Katagiri S, Yokoi T, Nishina S, Azuma N. Structure and morphology of radial retinal folds with familial exudative vitreoretinopathy. Ophthalmology. 2016;123(3)666-8. doi: 10.1016/j.ophtha.2015.09.010.
  6. Yaguchi Y, Katagiri S, Fukushima Y, Yokoi T, Nishina S, Kondo M, Azuma N. Electroretinographic effects of retinal dragging and retinal folds in eyes with familial exudative vitreoretinopathy. Sci Rep. 2016;6:30523. doi: 10.1038/srep30523.
  7. Okamoto-Uchida Y, Yu R, Miyamura N, Arima N, Ishigami-Yuasa M, Kagechika H, Yoshida S, Hosoya T, Nawa M, Kasama T, Asaoka Y, Alois RW, Elling U, Penninger JM, Nishina S, Azuma N, Nishina H. The mevalonate pathway regulates primitive streak formation via protein farnesylation. Sci Rep 2016;6:37697. doi: 10.1038/srep37697.
  8. Katagiri S, Tanaka S, Yokoi T, Hayashi T, Matsuzaka E, Ueda K, Yoshida-Uemura T, Arakawa A, Nishina S, Kadonosono K, Azuma N. Clinical features of a toddler with bilateral bullous retinoschisis with a novel RS1 mutation. Am J Ophthalmol Case Rep. 2016; ;5:76-80. doi: 10.1016/j.ajoc.2016.12.009.

2015

  1. Tanaka T, Yokoi T, Tamalu F, Watanabe S, Nishina S, Azuma N. Generation of retinal ganglion cells with functional axons from human induced pluripotent stem cells. Sci. Rep. 2015 Feb 10;5:8344. doi: 10.1038/srep08344.
  2. Nagamoto T, Oshika T, Fujikado T, Ishibashi T, Sato M, Kondo M, Kurosaka D, Azuma N. Clinical characteristics of congenital and developmental cataract undergoing surgical treatment. Jpn J Ophthalmol. 2015;59:148-156.doi: 10.1007/s10384-015-0370-8
  3. Nagamoto T, Oshika T, Fujikado T, Ishibashi T, Sato M, Kondo M, Kurosaka D, Azuma N. A survey of the surgical treatment of congenital and developmental cataracts in Japan. Jpn J Ophthalmol. 2015;59:203-208. https://doi.org/10.1007/s10384-015-0385-1
  4. Yokoi T, Nakayama Y, Nishina S, Azuma N. Abnormal traction of the vitreous detected by swept-source optical coherence tomography is related to the maculopathy associated with optic disc pits. Graefes Arch Clin Exp Ophthalmol. 2016; 254(4):675-682. doi: 10.1007/s00417-015-3114-z.
  5. Yokoi T, Nishina S, Fukami M, Ogata T, Hosono K, Hotta Y, Azuma N. Genotype-Phenotype Correlation of the PAX6 Gene Mutations in Aniridia. Hum Genome Var 2016; 3:15052. doi: 10.1038/hgv.2015.52.