Department of Ophthalmology,Kyushu University Hospital.

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Ocular Inflammation Group

Elucidation of pathogenesis of autoimmune uveitis.

P.I.;Koh-Hei Sonoda , Eiichi Hasegawa

Uveitis is one of the refractory eye diseases leading cause of severe loss of vision. It is defined as inflammation of the uvea, which has infectious or non-infectious causes. The precise immunologic mechanisms of uveitis with systemic or autoimmune diseases still remain unclear.
Our research group has shown that both Th1 and Th17 cells are responsible for the pathogenesis of uveitis using the rodent model of uveitis (Experimental Autoimmune Uveitis: EAU). (Sonoda KH et al. Acta Ophthalmol. 2011; Yoshimura T et al. Rheumatology 2009; Yoshimura T et al. Int Immunol. 2008). We recently elucidated that inflammatory cytokines (Takeda A et al. Exp Eye Res. 2014) and T cell signaling (Takeda A et al. Lab Invest. 2018) are related to the pathogenesis of uveitis. Interleukin (IL)-27 and IL-35 are inflammatory cytokines and Epstein-Barr virus-induced gene 3 (EBI3) is a component of IL-27 and IL-35. When EBI3-/- mice were induced EAU, both the clinical and histological analyses revealed that uveitis in EBI3-/- mice were diminished compared with those in control mice (Figure 1). We also showed that EBI3 controls Th1 cell and Th17 cell responses in EAU (Figure 2). In T cells, ATP, which is released by CD4+ T cells upon T cell receptor stimulation, binds to P2X7 receptor (P2RX7) to initiate T cell activation and proliferation. The severity of EAU scores in P2rx7-/- mice was reduced as compared with that in control mice. Histological analysis also showed lower inflammation in P2rx7-/- mice. The induction of IFN-γ and IL-17 in P2rx7−∕−mice was lower than that in control mice. These results suggest that ATP-P2RX7 signaling can exacerbates inflammation in uveitis. Currently, we are seeking novel morbidity marker from the aqueous humor, vitreous and serum samples of patients with uveitis.


  • Figure 1


  • Figure 2

Analysis of roles of inflammatory cells and cytokines in inflammatory ocular diseases

Our group is also focusing on inflammatory pathology other than Uveitis, such as choroidal neovascularization or fibrosis in Age-related macular degeneration (AMD). Our research targets are inflammatory cells and inflammatory cytokines in those inflammatory ocular diseases. We demonstrated that IL-17, which is a major proinflammatory cytokine, had a strong potential for promoting intraocular neovascularization (Figure 3). Although Th17 is well known as the main source of IL-17, we identified infiltrated γδT cells, but not Th17 cells, were the main source of IL-17 in experimental intraocular neovascularization (Hasegawa et al. J Immunol. 2013). Also, we elucidated that metabolites of unsaturated fatty acids are responsible for regression of intraocular neovessels, which work in part by modulating the recruitment of inflammatory immune cells such as macrophages (Hasegawa et al. Proc Natl Acad Sci. 2017). We also targeted subretinal fibrosis, which is frequently observed in advanced AMD. We have established new rodent model of subretinal fibrosis (Figure 4) (Jo YJ. IOVS. 2011) and elucidated several inflammatory cytokines were involved in the pathogenesis of fibrosis (Zhang H. PLoS One. 2013, Yang Y. PLoS One. 2013). Our goal is to find novel therapeutic targets and provide novel remedy for inflammatory ocular diseases.


  • Figure 3


  • Figure 4

Selected publications

  • Crucial role of P2X7 receptor for effector T cell activation in experimental autoimmune uveitis.
    Takeda A, Yamada H, Hasegawa E, Arima M, Notomi S, Myojin S, Yoshimura T, Hisatomi T, Enaida H, Yanai R, Kimura K, Ishibashi T, Sonoda KH.
    Jpn J Ophthalmol. 2018 May;62(3):398-406. doi: 10.1007/s10384-018-0587-4. Epub 2018 Mar 23.
  • Cytochrome P450 monooxygenase lipid metabolites are significant second messengers in the resolution of choroidal neovascularization.
    Hasegawa E, Inafuku S, Mulki L, Okunuki Y, Yanai R, Smith KE, Kim CB, Klokman G, Bielenberg DR, Puli N, Falck JR, Husain D, Miller JW, Edin ML, Zeldin DC, Lee KSS, Hammock BD, Schunck WH, Connor KM.
    Proc Natl Acad Sci U S A. 2017 Sep 5;114(36):E7545-E7553. doi: 10.1073/pnas.1620898114. Epub 2017 Aug 21.
  • Epidemiology of Uveitis, Caused by HTLV-1, Toxoplasmosis, and Tuberculosis; the Three Leading Causes of Endemic Infectious Uveitis in Japan.
    Takeda A, Ishibashi T, Sonoda KH.
    Ocul Immunol Inflamm. 2017;25(sup1):S19-S23. doi: 10.1080/09273948.2016.1253851. Epub 2016 Dec 7. Review.
  • Gene Expression Analysis of the Irrigation Solution Samples Collected during Vitrectomy for Idiopathic Epiretinal Membrane.
    Myojin S, Yoshimura T, Yoshida S, Takeda A, Murakami Y, Kawano Y, Oshima Y, Ishibashi T, Sonoda KH.
    PLoS One. 2016 Oct 13;11(10):e0164355. doi: 10.1371/journal.pone.0164355. eCollection 2016.
  • Pathogenic Function of Herpesvirus Entry Mediator in Experimental Autoimmune Uveitis by Induction of Th1- and Th17-Type T Cell Responses.
    Sakoda Y, Nagai T, Murata S, Mizuno Y, Kurosawa H, Shoda H, Morishige N, Yanai R, Sonoda KH, Tamada K.
    J Immunol. 2016 Apr 1;196(7):2947-54. doi: 10.4049/jimmunol.1501742. Epub 2016 Feb 24.
  • Distinct Profiles of Soluble Cytokine Receptors Between B-Cell Vitreoretinal Lymphoma and Uveitis.
    Takeda A, Yoshikawa H, Fukuhara T, Hikita S, Hijioka K, Otomo T, Arita R, Hisatomi T, Kimura K, Yoshida S, Kawano Y, Sonoda KH, Ishibashi T.
    Invest Ophthalmol Vis Sci. 2015 Nov;56(12):7516-23. doi: 10.1167/iovs.15-17465.
  • Dietary Omega-3 Fatty Acids Suppress Experimental Autoimmune Uveitis in Association with Inhibition of Th1 and Th17 Cell Function.
    Shoda H, Yanai R, Yoshimura T, Nagai T, Kimura K, Sobrin L, Connor KM, Sakoda Y, Tamada K, Ikeda T, Sonoda KH.
    PLoS One. 2015 Sep 22;10(9):e0138241. doi: 10.1371/journal.pone.0138241. eCollection 2015.
  • EBI3 is pivotal for the initiation of experimental autoimmune uveitis.
    Takeda A, Hasegawa E, Fukuhara T, Hirakawa S, Yamada H, Yang Y, Yoshimura T, Hisatomi T, Oshima Y, Yoshida H, Sonoda KH, Ishibashi T.
    Exp Eye Res. 2014 Aug;125:107-13. doi: 10.1016/j.exer.2014.06.004. Epub 2014 Jun 11.
    IL-10 is significantly involved in HSP70-regulation of experimental subretinal fibrosis.
    Yang Y, Takeda A, Yoshimura T, Oshima Y, Sonoda KH, Ishibashi T.
    PLoS One. 2013 Dec 20;8(12):e80288. doi: 10.1371/journal.pone.0080288. eCollection 2013. Erratum in: PLoS One. 2014;9(3):e91197.
    A Novel Platelet-Activating Factor Receptor Antagonist Inhibits Choroidal Neovascularization and Subretinal Fibrosis.
    Zhang H, Yang Y, Takeda A, Yoshimura T, Oshima Y, Sonoda KH, Ishibashi T.
    PLoS One. 2013 Jun 27;8(6):e68173. doi: 10.1371/journal.pone.0068173. Print 2013.
  • IL-23-independent induction of IL-17 from γδT cells and innate lymphoid cells promotes experimental intraocular neovascularization.
    Hasegawa E, Sonoda KH, Shichita T, Morita R, Sekiya T, Kimura A, Oshima Y, Takeda A, Yoshimura T, Yoshida S, Ishibashi T, Yoshimura A.
    J Immunol. 2013 Feb 15;190(4):1778-87. doi: 10.4049/jimmunol.1202495. Epub 2013 Jan 14.
  • IL-27 inhibits pathophysiological intraocular neovascularization due to laser burn.
    Hasegawa E, Oshima Y, Takeda A, Saeki K, Yoshida H, Sonoda KH, Ishibashi T.
    J Leukoc Biol. 2012 Feb;91(2):267-73. doi: 10.1189/jlb.1110603. Epub 2011 Nov 1.
  • Acquired resistance to infliximab against uveitis due to Behçet's disease after one year of administration.
    Ito T, Sonoda KH, Hijioka K, Fujimoto T, Ishibashi T.
    Jpn J Ophthalmol. 2010 Sep;54(5):502-4. doi: 10.1007/s10384-010-0859-0. Epub 2010 Nov 5. No abstract available.
  • Establishment of a new animal model of focal subretinal fibrosis that resembles disciform lesion in advanced age-related macular degeneration.
    Jo YJ, Sonoda KH, Oshima Y, Takeda A, Kohno R, Yamada J, Hamuro J, Yang Y, Notomi S, Hisatomi T, Ishibashi T.
    Invest Ophthalmol Vis Sci. 2011 Aug 1;52(9):6089-95. doi: 10.1167/iovs.10-5189.
  • Neutrophil-dominant experimental autoimmune uveitis in CC-chemokine receptor 2 knockout mice.
    Sonoda KH, Yoshimura T, Egashira K, Charo IF, Ishibashi T.
    Acta Ophthalmol. 2011 Mar;89(2):e180-8. doi: 10.1111/j.1755-3768.2010.01953.x.
  • Choroidal neovascularization enhanced by Chlamydia pneumoniae via Toll-like receptor 2 in the retinal pigment epithelium.
    Fujimoto T, Sonoda KH, Hijioka K, Sato K, Takeda A, Hasegawa E, Oshima Y, Ishibashi T.
    Invest Ophthalmol Vis Sci. 2010 Sep;51(9):4694-702. doi: 10.1167/iovs.09-4464. Epub 2010 Apr 14.
  • Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases.
    Yoshimura T, Sonoda KH, Sugahara M, Mochizuki Y, Enaida H, Oshima Y, Ueno A, Hata Y, Yoshida H, Ishibashi T.
    PLoS One. 2009 Dec 4;4(12):e8158. doi: 10.1371/journal.pone.0008158.
  • Involvement of Th17 cells and the effect of anti-IL-6 therapy in autoimmune uveitis.
    Yoshimura T, Sonoda KH, Ohguro N, Ohsugi Y, Ishibashi T, Cua DJ, Kobayashi T, Yoshida H, Yoshimura A.
    Rheumatology (Oxford). 2009 Apr;48(4):347-54. doi: 10.1093/rheumatology/ken489. Epub 2009 Jan 22.

Ocular Fibrosis Group

P.I.;Keijiro Ishikawa

1. Development of molecular-targeting therapies for intraocular proliferative
diseases including Diabetic retinopathy, Proliferative vitreoretinopathy and Age-related macular degeneration

Intraocular proliferative diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR) are a leading cause of decreased vision and blindness in Japan. In those diseases, retinal fibro(vascular) membrane formation above and beneath the retina plays a pivotal role in the primary pathology (Figure 1).
In order to identify genes responsible for intraocular proliferation, we first determined the gene expression profiling of human retina, ERMs associated with proliferative diabetic retinopathy (PDR-ERMs), and PVR (PVR-ERMs) (Figure 2). We next determined "highly expressed genes in PDR- and in PVR-ERMs" by comparing the gene expression profiles between PDR-, PVR-ERMs and the retina. Subsequent analyses identified matricellular proteins, including periostin and tenascin C as important molecules whose expressions are enhanced specifically in proliferating ERMs compared to the retina (Ishikawa K et al. IOVS 2015).
We found increased periostin and tenascin C expression in the vitreous of patients with both PDR and PVR. Immunohistochemical analysis showed colocalization of periostin and α-SMA in PDR- and PVR-ERMs (Kobayashi Y et al. Mol Vis 2016; Ishikawa K et al. FASEB J 2014; Yoshida S et al. IOVS 2012). In vitro, both periostin and tenascin C increased proliferation, adhesion, migration and collagen production in RPE cells. Periostin blockade suppressed migration and adhesion induced by transforming growth factor-β2 (TGF-β2) and PVR vitreous. In vivo, periostin and tenascin C inhibition had the inhibitory effect on experimental retinal and choroidal fibrovascular formation, and progression of experimental PVR without affecting the viability of retinal cells (Kobayashi Y et al. Lab Invest 2016; Ishikawa K et al. FASEB J 2014). These results identified periostin and tenascin C as a pivotal molecule for fibro(vascular) formation. Thus, developing the novel antibody and/or innovative could be a potential therapeutic strategy for inhibiting the progression of intraocular proliferative diseases including DR and AMD.

2. Exploration of the underlying mechanisms in EMT of RPE;Establishment of EMT targeting therapy to prevent fibrosis associated with AMD and PVR.

In the pathogenesis of intraocular fibrosis associated with AMD and PVR, epithelial to mesenchymal transition (EMT) of RPE is one of the important steps; that is, RPE that undergo EMT acquire a fibroblast phenotype with increased capacity to proliferate and migrate and with the ability to produce ECM, which facilitate the formation of fibrotic membrane (Ishikawa K et al. Am J Pathol. 2016). Our comprehensive gene expression analyses of surgically resected human fibrous membranes associated with PDR and PVR revealed the significant EMT-related molecules (Ishikawa K et al. IOVS 2015).
We study the underlying mechanisms in EMT of RPE by investigating the expression and functions of those EMT-related molecules in human samples and/or the animal models of both pre- and subretinal fibrosis (rabbit PVR model and mouse laser-induced CNV model) by real-time PCR, ELISA, Western blot and IHC, etc (Figure 3) (Ishikawa K et al. Sci Rep. 2015; Ishikawa K et al. Exp Eye Res. 2016). Moreover, we explore the biological function and the underlying molecular pathways related to EMT in vitro and seek to establish EMT targeting therapy to prevent fibrosis associated with AMD and PVR (Figure 4).

  • Human samples or clinical information can be collected after approval by the Ethics Committee of the Kyushu University Hospital, and obtainment of informed consent for the surgery and the use of specimens from patients. The expression of the molecules can be examined using those surgically-resected specimens and vitreous samples.
  • The pathways mediated by those molecules can be further examined by in vitro assay using primary RPE cells.
  • Check the inhibitory effect of those molecules in both animal models, and determine whether the molecules can be novel therapeutic targets.
  • Figure 1

  • Figure 2

  • Figure 3

  • Figure 4

Selected publications

  • Leukotriene B4 promotes neovascularization and macrophage recruitment in murine wet-type AMD models.
    Sasaki F, Koga T, Ohba M, Saeki K, Okuno T, Ishikawa K, Nakama T, Nakao S, Yoshida S, Ishibashi T, Ahmadieh H, Kanavi MR, Hafezi-Moghadam A, Penninger JM, Sonoda KH, Yokomizo T.
    JCI Insight. 2018; Sep 20;3(18).
  • Periostin in vitreoretinal diseases.
    Yoshida S, Nakama T, Ishikawa K, Nakao S, Sonoda KH, Ishibashi T.
    Cell Mol Life Sci. 2017; Dec;74(23):4329-4337.
  • αB-crystallin regulates subretinal fibrosis by modulation of epithelial-mesenchymal transition.
    Ishikawa K, Sreekumar PG, Spee C, Nazari H, Zhu D, Kannan R, Hinton DR.
    Am J Pathol. 2016;186:859-73.
  • Molecular mechanisms of subretinal fibrosis in age-related macular degeneration.
    Ishikawa K, Kannan R, Hinton DR.
    Exp Eye Res. 2016;142:19-25.
  • Tenascin-C secreted by transdifferentiated retinal pigment epithelial cells promotes choroidal neovascularization via integrin alphaV.
    Kobayashi Y, Yoshida S, Zhou Y, Nakama T, Ishikawa K, Kubo Y, Arima M, Nakao S, Hisatomi T, Matsuda A, Sonoda KH, Ishibashi T.
    Lab Invest 2016;96:1178-1188.
  • Different roles played by periostin splice variants in retinal neovascularization.
    Nakama T, Yoshida S, Ishikawa K, Kobayashi Y, Abe T, Kiyonari H, Shioi G, Katsuragi N, Ishibashi T, Morishita R, Taniyama Y.
    Exp Eye Res 2016;153:133-140.
  • Comparison of the Effectiveness of Intravitreal Ranibizumab for Diabetic Macular Edema in Vitrectomized and Nonvitrectomized Eyes.
    Koyanagi Y, Yoshida S, Kobayashi Y, Kubo Y, Yamaguchi M, Nakama T, Nakao S, Ohshima Y, Ishibashi T, Sonoda KH.
    Ophthalmologica 2016;236:67-73.
  • Interleukin-12 inhibits pathological neovascularization in mouse model of oxygen-induced retinopathy.
    Zhou Y, Yoshida S, Kubo Y, Kobayashi Y, Nakama T, Yamaguchi M, Ishikawa K, Nakao S, Ishibashi T, Sonoda KH.
    Sci Rep 2016;6:28140.
  • Tenascin-C promotes angiogenesis in fibrovascular membranes in eyes with proliferative diabetic retinopathy.
    Kobayashi Y, Yoshida S, Zhou Y, Nakama T, Ishikawa K, Arima M, Nakao S, Sassa Y, Takeda A, Hisatomi T, Matsuda A, Sonoda KH, Ishibashi T.
    Mol Vis 2016;22:436-445.
  • The kinetics of VEGF and MCP-1 in the second vitrectomy cases with proliferative diabetic retinopathy.
    Sassa Y, Yoshida S, Ishikawa K, Asato R, Ishibashi T, Kono T.
    Eye (Lond) 2016.30:746-753.
  • Reduced vitreal concentration of periostin after vitrectomy in patients with proliferative diabetic retinopathy.
    Tachibana T, Yoshida S, Kubo Y, Koayashi Y, Nakama T, Ishikawa K, Nakao S, Izuhara K, Kono T, Ishibashi T.
    Acta Ophthalmol 2016;94:e81-82.
  • Resveratrol inhibits epithelial-mesenchymal transition of retinal pigment epithelium and development of proliferative vitreoretinopathy.
    Ishikawa K, He S, Terasaki H, Nazari H, Zhang H, Spee C, Kannan R, Hinton DR.
    Sci Rep. 2015;10;5:16386.
  • M2 Macrophages Enhance Pathological Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy.
    Zhou Y, Yoshida S, Nakao S, Yoshimura T, Kobayashi Y, Nakama T, Kubo Y, Miyawaki K, Yamaguchi M, Ishikawa K, Oshima Y, Akashi K, Ishibashi T.
    Invest Ophthalmol Vis Sci 2015;56:4767-4777.
  • Differential improvement of vertical and horizontal metamorphopsia scores after epiretinal membrane vitrectomy with ILM peeling.
    Tachibana T, Yoshida S, Kobayashi Y, Nakama T, Ishikawa K, Sengoku A, Nakao S, Oshima Y, Ishibashi T.
    Acta Ophthalmol 2015;93:e681-682.
  • Increased vitreous concentrations of MCP-1 and IL-6 after vitrectomy in patients with proliferative diabetic retinopathy: possible association with postoperative macular oedema.
    Yoshida S, Kubo Y, Kobayashi Y, Zhou Y, Nakama T, Yamaguchi M, Tachibana T, Ishikawa K, Arita R, Nakao S, Sassa Y, Oshima Y, Kono T, Ishibashi T.
    Br J Ophthalmol 2015;99:960-966.
  • Microarray analysis of gene expression in fibrovascular membranes excised from patients with proliferative diabetic retinopathy.
    Ishikawa K, Yoshida S, Kobayashi Y, Zhou Y, Nakama T, Nakao S, Sassa Y, Oshima Y, Niiro H, Akashi K, Kono T, Ishibashi T.
    Invest Ophthalmol Vis Sci 2015;56:932-946.
  • Inhibition of choroidal fibrovascular membrane formation by new class of RNA interference therapeutic agent targeting periostin.
    Nakama T, Yoshida S, Ishikawa K, Kobayashi Y, Zhou Y, Nakao S, Sassa Y, Oshima Y, Takao K, Shimahara A, Yoshikawa K, Hamasaki T, Ohgi T, Hayashi H, Matsuda A, Kudo A, Nozaki M, Ogura Y, Kuroda M, Ishibashi T.
    Gene Ther 2015;22:127-137.
  • Increased expression of M-CSF and IL-13 in vitreous of patients with proliferative diabetic retinopathy: implications for M2 macrophage-involving fibrovascular membrane formation.
    Yoshida S, Kobayashi Y, Nakama T, Zhou Y, Ishikawa K, Arita R, Nakao S, Miyazaki M, Sassa Y, Oshima Y, Izuhara K, Kono T, Ishibashi T.
    Br J Ophthalmol 2015;99:629-634.
  • Overexpression of CD163 in vitreous and fibrovascular membranes of patients with proliferative diabetic retinopathy: possible involvement of periostin.
    Kobayashi Y, Yoshida S, Nakama T, Zhou Y, Ishikawa K, Arita R, Nakao S, Miyazaki M, Sassa Y, Oshima Y, Izuhara K, Kono T, Ishibashi T.
    Br J Ophthalmol 2015;99:451-456.
  • Periostin promotes the generation of fibrous membranes in proliferative vitreoretinopathy.
    Ishikawa K, Yoshida S, Nakao S, Nakama T, Kita T, Asato R, Sassa Y, Arita R, Miyazaki M, Enaida H, Oshima Y, Murakami N, Niiro H, Ono J, Matsuda A, Goto Y, Akashi K, Izuhara K, Kudo A, Kono T, Hafezi-Moghadam A, Ishibashi T.
    FASEB J 2014;28:131-142.
  • Comparison of gene expression profile of epiretinal membranes obtained from eyes with proliferative vitreoretinopathy to that of secondary epiretinal membranes.
    Asato R, Yoshida S, Ogura A, Nakama T, Ishikawa K, Nakao S, Sassa Y, Enaida H, Oshima Y, Ikeo K, Gojobori T, Kono T, Ishibashi T.
    PLoS One 2013;8:e54191.
  • Antiangiogenic shift in vitreous after vitrectomy in patients with proliferative diabetic retinopathy.
    Yoshida S, Nakama T, Ishikawa K, Arima M, Tachibana T, Nakao S, Sassa Y, Yasuda M, Enaida H, Oshima Y, Kono T, Ishibashi T.
    Invest Ophthalmol Vis Sci 2012;53:6997-7003.
  • Involvement of periostin in regression of hyaloidvascular system during ocular development.
    Arima M, Yoshida S, Nakama T, Ishikawa K, Nakao S, Yoshimura T, Asato R, Sassa Y, Kita T, Enaida H, Oshima Y, Matsuda A, Kudo A, Ishibashi T.
    Invest Ophthalmol Vis Sci 2012;53:6495-6503.
  • Bone marrow-derived monocyte lineage cells recruited by MIP-1beta promote physiological revascularization in mouse model of oxygen-induced retinopathy.
    Ishikawa K, Yoshida S, Nakao S, Sassa Y, Asato R, Kohno R, Arima M, Kita T, Yoshida A, Ohuchida K, Ishibashi T.
    Lab Invest 2012;92:91-101.
  • Increased expression of periostin in vitreous and fibrovascular membranes obtained from patients with proliferative diabetic retinopathy.
    Yoshida S, Ishikawa K, Asato R, Arima M, Sassa Y, Yoshida A, Yoshikawa H, Narukawa K, Obika S, Ono J, Ohta S, Izuhara K, Kono T, Ishibashi T.
    Invest Ophthalmol Vis Sci 2011;52:5670-5678.
  • Gene expression profile of hyperoxic and hypoxic retinas in a mouse model of oxygen-induced retinopathy.
    Ishikawa K, Yoshida S, Kadota K, Nakamura T, Niiro H, Arakawa S, Yoshida A, Akashi K, Ishibashi T.
    Invest Ophthalmol Vis Sci 2010;51:4307-4319.
  • Reduced concentrations of angiogenesis-related factors in vitreous after vitrectomy in patients with proliferative diabetic retinopathy.
    Yoshida S, Ishikawa K, Matsumoto T, Yoshida A, Ishibashi T, Kono T.
    Graefes Arch Clin Exp Ophthalmol 2010;248:799-804.
  • Gene expression profile of fibrovascular membranes from patients with proliferative diabetic retinopathy.
    Yoshida S, Ogura A, Ishikawa K, Yoshida A, Kohno R, Yamaji Y, Ikeo K, Gojobori T, Kono T, Ishibashi T.
    Br J Ophthalmol 2010;94:795-801.
  • TEM7 (PLXDC1) in neovascular endothelial cells of fibrovascular membranes from patients with proliferative diabetic retinopathy.
    Yamaji Y, Yoshida S, Ishikawa K, Sengoku A, Sato K, Yoshida A, Kuwahara R, Ohuchida K, Oki E, Enaida H, Fujisawa K, Kono T, Ishibashi T.
    Invest Ophthalmol Vis Sci 2008;49:3151-3157.

Gene Therapy Group

P.I.;Yusuke Murakami

1. Neuroprotective gene therapy for patients with retinitis pigmentosa

 Retinitis pigmentosa (RP) is a major cause of blindness, affecting approximately 1 in about 5,000 people pan-ethnically. RP is caused by mutations in various genes (more than 70 responsible genes), including the rhodopsin and cGMP phosphodiesterase 6 (PDE6b) genes. However, the biological processes by which these mutations lead to progressive photoreceptor death are still unclear and no effective treatment exists for RP. One of the common pathology in genetically heterogenous RP is “apoptosis” of the photoreceptor cells. We have conducted translational research to apply neuroprotective gene therapy using an original viral vector carrying pigment epithelium-derived factor (PEDF) gene to prevent photoreceptor cell apoptosis.
 Previously, we demonstrated an efficient and stable retinal gene transfer mediated by the non-pathogenic simian immunodeficiency virus from African green monkeys (SIVagm)-based lentiviral vector in rodent and non-human primate retinas (et al. Gene Ther. 2003; et al. Hum Gene Ther. 2009a.), and the therapeutic outcome in animal models of retinal degeneration using recombinant SIVagm-based lentiviral vectors carrying human PEDF gene (Miyazaki M, et al. Gene Ther. 2003; Miyazaki M, et al. J Gene Med. 2008; Murakami Y, et al. Am J Pathol. 2008.). We also reported the systemic and local effects following intraocular administration of SIV-hPEDF in Macaca fascicularis, as a preclinical safety study (et al. Hum Gene Ther. 2009b.).
 Based on our efficacy studies and safety studies, a clinical study (UMIN000010260) to assess the safety of subretinal administration of SIV-hPEDF has already finished. The first subject was enrolled on March 26th, 2013 and gene transfer was done in five subjects in the low titer group (2.5 x 107 transducing units [TU]/mL). No serious adverse event caused by gene transfer was detected in all subjects in the observation period (24 months). We are now going to conduct an investigator initiated clinical trial (Phase I/IIa) (UMIN000034081) aimed at establishing this strategy as the next-generation standard treatment.

Selected publications

  • MUTYH promotes oxidative microglial activation and inherited retinal degeneration.
    Nakatake S, Murakami Y, Morioka N, Tachibana T, Fujiwara K, Yoshida N, Notomi S, Hisatomi T, Yoshida S, Ishibashi T, Nakabeppu Y, Sonoda KH.
    JCI Insight. 1: e87781, 2016.
  • Association Between Aqueous Flare and Epiretinal Membrane in Retinitis Pigmentosa.
    Fujiwara K, Murakami Y, Nakatake S, Tachibana T, Yoshida N, Nakao S, Hisatomi T, Yoshida S, Yoshitomi T, Sonoda KH, Ishibashi T.
    Invest Ophthalmol Vis Sci. 57: 4282-4286, 2016.
  • Necrotic cone photoreceptor cell death in retinitis pigmentosa.
    Murakami Y, Nakatake S, Miller JW, Vavvas DG, Sonoda KH, Ishibashi T.
    Cell Death Dis. 6:e2038, 2015.
  • Vitreous cysts in patients with retinitis pigmentosa.
    Yoshida N, Murakami Y, Nakatake S, Takashi T, Notomi S, Hisatomi T, Ishibashi T.
    Jpn J Ophthalmol. 59:373-377, 2015.
  • Long-term Surgical Outcomes of Epiretinal Membrane in Patients with Retinitis Pigmentosa.
    Yoshida N (equal contribution), Murakami Y, Nakatake S, Notomi S, Hisatomi T, Enaida H, Ishibashi T.
    Sci Rep.5;13078, 2015.
  • Correlation between macular blood flow and central visual sensitivity in retinitis pigmentosa.
    Murakami Y, Akiyama M, Fujiwara K, Yoshida N, Nakatake S, Notomi S, Nabeshima T, Hisatomi T, Enaida H, Ushibashi T.
    Acta Ophthalmol. 93:e644-648, 2015.
  • Factors affecting visual acuity after cataract surgery in patients with retinitis pigmentosa.
    Yoshida N, Murakami Y, Nakatake S, Fujiwara K, Notomi S, Hisatomi T, Ishibashi T.
    Ophthalmology 122:903-908, 2015.
  • Factors affecting visual acuity after cataract surgery in patients with retinitis pigmentosa.
    Yoshida N, Murakami Y, Nakatake S, Fujiwara K, Notomi S, Hisatomi T, Ishibashi T.
    Ophthalmology 122:903-908, 2015.
  • Relationship between aqueous flare and visual function in retinitis pigmentosa.
    Murakami Y, Yoshida N, Nakatake S, Fujiwara K, Notomi S, Nabeshima T, Nakao S, Hisatomi T, Enaida H, Ishibashi T.
    Am J Ophthalmol. 159:958-963, 2015.
  • Development and evaluation of the visual aid using see-through display for patients with retinitis pigmentosa.
    Suzuki E, Kuramata T, Kozaki T, Koyama T, Kato Y, Enaida H, Ishibashi T.
    Jpn J Ophthalmol. 59: 43-47, 2015.
  • Therapeutic efficacy of topical unoprostone isopropyl in retinitis pigmentosa.
    Akiyama M, Yoshida N, Notomi S, Murakami Y, Hisatomi T, Enaida H, Ishibashi T.
    Acta Ophthalmol. 92: e229-234, 2014.
  • Therapeutic effect of prolonged treatment with topical dorzolamide for cystoid macular oedema in patients with retinitis pigmentosa.
    Yoshida N, Notomi S, Murakami Y, Hisatomi T, Enaida H, Ishibashi T.
    Br J Ophthalmol. 97:1187-1191, 2013.
  • Laboratory evidence of sustained chronic inflammatory reaction in Retinitis Pigmentosa.
    Yoshida N, Notomi S, Ishikawa K, Murakami Y, Hisatomi T, Enaida H, Ishibashi T.
    Ophthalmology 120:e5-12, 2013.
  • Clinical evidence of sustained chronic inflammatory reaction in Retinitis Pigmentosa.
    Yoshida N, Notomi S, Ishikawa K, Murakami Y, Hisatomi T, Enaida H, Ishibashi T.
    Ophthalmology 120:100-105, 2013.
  • Receptor interacting protein kinase mediates necrotic cone but not rod cell death in a mouse model of inherited degeneration.
    Murakami Y, Matsumoto H, Roh M, Suzuki J, Hisatomi T, Miller JW, Vavvas DG.
    Proc Natl Acad Sci U S A. 109:14598-14603, 2012.
  • MutT Homolog-1 Attenuates Oxidative DNA Damage and Delays Photoreceptor Cell Death in Inherited Retinal Degeneration.
    Murakami Y, Yoshida N, Notomi S, Hisatomi T, Oka S, De Luca G, Yonemitsu Y, Bignami M, Nakabeppu Y, Ishibashi T.
    Am J Pathol. 181:1378-1386, 2012.
  • The Clinical Efficacy of a Topical Dorzolamide in the Management of Cystoid Macular Edema in Patients with Retinitis Pigmentosa.
    Hisatomi T, Yoshida N, Notomi S, Murakami Y, Enaida H, and Ishibashi T.
    Graefes Arch Clin Exp Ophthalmol. 250:809-814, 2012.
  • PEDF gene therapy targeting retinal ganglion cell injuries: neuroprotection against loss of function in two animal models.
    Miyazaki M, Yonemitsu Y, Goto Y, Murakami Y, Yoshida N, Tabata T, Hasegawa M, Tobimatsu S, Sueishi K, Ishibashi T.
    Hum Gene Ther. 22:559-565, 2011.
  • PEDF gene therapy targeting retinal ganglion cell injuries: neuroprotection against loss of function in two animal models.
    Miyazaki M, Yonemitsu Y, Goto Y, Murakami Y, Yoshida N, Tabata T, Hasegawa M, Tobimatsu S, Sueishi K, Ishibashi T.
    Hum Gene Ther. 22:559-565, 2011.
  • Acute Toxicity Study of a Simian Immunodeficiency Virus-based Lentiviral Vector for Retinal Gene Transfer in Nonhuman Primates.
    Yonemitsu Y, Miyazaki M, Kohno RI, Murakami Y, Murata T, Goto Y, Tabata T, Ueda Y, Ono F, Suzuki T, Ageyama N, Terao K, Hasegawa M, Sueishi K, Ishibashi T.
    Hum Gene Ther. 20:943-954, 2009.
  • Stable Retinal Gene Expression in Nonhuman Primates via Subretinal Injection of SIVagm-based Lentiviral Vectors.
    Yonemitsu Y, Miyazaki M, Kohno RI, Murakami Y, Murata T, Tabata T, Ueda Y, Ono F, Suzuki T, Ageyama N, Terao K, Hasegawa M, Sueishi K, Ishibashi T.
    Hum Gene Ther. 20:573-576, 2009.
  • Inhibition of nuclear translocation of apoptosis-inducing factor is an essential mechanism of the neuroprotective activity of pigment epithelium-derived factor in a rat model of retinal degeneration.
    Murakami Y, Yonemitsu Y, Onimaru M, Nakagawa K, Kohno R, Miyazaki M, Hisatomi T, Nakamura M, Yabe T, Hasegawa M, Ishibashi T, Sueishi K.
    Am J Pathol. 173:1326-1338, 2008.
  • Synergistic neuroprotective effect via simian lentiviral vector-mediated simultaneous gene transfer of human pigment epithelium-derived factor and human fibroblast growth factor-2 in rodent models of retinitis pigmentosa.
    Miyazaki M, Yonemitsu Y, Goto Y, Kohno RI, Murakami Y, Inoue M, Ueda Y, Hasegawa M, Tobimatsu S, Sueishi K, Ishibashi T.
    J Gene Med. 10:1273-1281, 2008.
  • Simian lentiviral vector-mediated retinal gene transfer of pigment epithelium-derived factor protects retinal degeneration and electrical defect in Royal College of Surgeons rats.
    Miyazaki M, Yonemitsu Y, Goto Y. Sakamoto T, Tabata T, Ueda Y, Hasegawa M, Tobimatsu S, Ishibashi T, Sueishi K.
    Gene Ther. 10:1503-1511, 2003.
  • Simian Immunodeficiency Virus-Based Lentiviral Vector For Retinal Gene Transfer: a preclinical safety study in adult rats.
    Goto Y, Yonemitsu Y, Miyazaki M, Sakamoto T, Ishibashi T, Ueda Y, Hasegawa M, Tobimatsu S, Sueishi K.
    Gene Ther. 10:1161-1169, 2003.

Retinal Imaging and Vascular Biology Group

P.I.;Shintarou Nakao

Welcome to the Department of Ophthalmology, Kyushu University Hospital’s “Imaging Group” site. Here you will find information about the research being conducted by our faculty. Our group is under the leadership of Assistant Professor, Shintaro Nakao MD.,PhD.
Our Research area includes: Understanding of vitreoretinal diseases; Vascular biology; Macrophages in vitreoretinal diseases; Development of novel therapeutic agents; Retinal imaging.
Our group also provides an excellent training environment for graduate students at the University of Kyushu. Current members in our group refer to the following site.
The purpose of our group is “connect” real world in clinic and molecular world in lab with imaging. By the result of our research, we can connect the clinical disease with the basic results, molecular mechanism, and new therapeutic target.
Please explore our site to learn more about the research being performed in each laboratory. Thank you for taking the time to visit us today!

Selected publications

Ocular Tumor and Genomics Group

PIs:Mika Tanabe , and Masato Akiyama

Ocular tumor is the life-threatening disease. Our department is one of the specialized institutions for the diagnosis and treatment of ocular tumors in Japan. In the Kyushu university hospital, we treat ocular tumors including orbital tumors, lacrimal gland tumors, eyelid tumors, conjunctival tumors, and intraocular tumors. The number of new cases with ocular tumors is about 250 cases per year. As well as the clinical practice, we are conducting basic research.
Recent advantages in genomic analysis expand our understandings of cancer genomes. These studies can provide us with a novel approach for the selection of the treatment drugs, and sub-classifications of the tumors based on molecular level information. Nevertheless, genomic analyses have been performed in a few tumors in the ophthalmologic field. We have started the genomic analysis of the ocular tumors by comprehensive DNA and RNA sequencing using the next-generation sequencer.
We have also launched a new project using the artificial intelligence (AI). Since the majority of the ocular tumors were rare, the diagnosis of ocular tumor is not easy for the family doctors and general ophthalmologists. Now, our department have the computational server which contains graphic processing units (GPU) in order to develop a deep learning system for the precise diagnosis of ocular tumors.

Selected publications

  • Cataracts after Low-Dose Radiotherapy for Lymphoproliferative Disease of the Ocular Adnexa.
    Hashimoto S, Yoshikawa H, Miyagi M, Onishi Y, Ohga S, Asai K, Ishibashi T.
    Semin Ophthalmol. 2016 Jul 15:1-5.
  • Clinical Features of Systemic Metastatic Retinal Lymphoma in Japanese Patients.
    Taki R, Takeda A, Yoshikawa H, Fukuhara T, Arita R, Suehiro Y, Choi I, Kumano Y, Nakamura T, Ishibashi T.
    Ocul Immunol Inflamm. 2016 Apr 12:1-9.
  • Distinct Profiles of Soluble Cytokine Receptors Between B-Cell Vitreoretinal Lymphoma and Uveitis.
    Takeda A, Yoshikawa H, Fukuhara T, Hikita S, Hijioka K, Otomo T, Arita R, Hisatomi T, Kimura K, Yoshida S, Kawano Y, Sonoda KH, Ishibashi T.
    Invest Ophthalmol Vis Sci. 2015 Nov;56(12):7516-23. doi: 10.1167/iovs.15-17465.
  • Ocular surface squamous neoplasia: analysis of 34 cases.
    Tanabe M, Yoshikawa H, Onishi Y, Kohno R, Ishibashi T.
    Nippon Ganka Gakkai Zasshi. 2014 May;118(5):425-32. Japanese.
  • A case of Muir-Torre syndrome with multiple cancers of bilateral eyelids and breast.
    Kamisasanuki T, Uchino E, Fukushima J, Yoshikawa H, Ishibashi T, Sakamoto T.
    Korean J Ophthalmol. 2013 Jun;27(3):204-7. doi: 10.3341/kjo.2013.27.3.204.
  • A case of metastatic choroidal tumor simulating a choroidal melanoma.
    Arima M, Yoshikawa H, Kagimoto T, Kohno R, Ishibashi T.
    Jpn J Ophthalmol. 2011 May;55(3):312-4. doi: 10.1007/s10384-011-0015-5.
  • Congenital simple hamartoma of the retinal pigment epithelium in an Asian.
    Gotoh M, Yoshikawa H, Kagimoto HT, Ishibashi T.
    Jpn J Ophthalmol. 2008 Mar-Apr;52(2):144-5. doi: 10.1007/s10384-008-0509-y.
  • Retinal capillary hemangioma managed by transpupillary thermotherapy.
    Mochizuki Y, Noda Y, Enaida H, Hata Y, Ueno A, Yoshikawa H, Ishibashi T.
    Retina. 2004 Dec;24(6):981-4.
  • Bilateral epiretinal membranes in nevoid basal cell carcinoma syndrome.
    Yoshida S, Yoshikawa H, Yoshida A, Nakamura T, Noda Y, Gondoh H, Fukagawa S, Moroi Y, Urabe K, Furue M, Ishibashi T.
    Acta Ophthalmol Scand. 2004 Aug;82(4):488-90.
  • Conjunctival keratoacanthoma in an Asian.
    Kifuku K, Yoshikawa H, Sonoda KH, Kawano Y, Miyazaki K, Ishibashi T.
    Arch Ophthalmol. 2003 Jan;121(1):118-9.

Hisayama Ophthalmic Epidemiology Group

P.I.;M Yasuda , K Fujiwara

The town of Hisayama is a suburb of Fukuoka city in Japan. The population rate increase of Japan from 1960 to 2010 is similar to that of Hisayama. Age distribution was almost the same across all age categories in both 1960 and 2010, similar to that of all of Japan. Moreover, distribution of the labor population was also similar between Japan nationally and Hisayama. Therefore, we can say that Hisayama’s population is a good sample for Japan as a whole.
The Hisayama Study is an ongoing, long-term cohort study on cardiovascular disease and its risk factors in the town of Hisayama. As a part of the overall study, an epidemiologic study of eye disease among residents of the town has been under way since 1998.
The purpose of our group is to clarify the prevalence, incidence and risk factors for common ocular disease, which cause visual impairment and vision loss, in a general Japanese population.
We started a new glaucoma incidence study from 2012-2013 in partnership with Oita and Akita universities. Several systemic and environmental factors related with the incidence of glaucoma are expected to be revealed.

Selected publications

  • Prevalence and risk factors for polypoidal choroidal vasculopathy in a general Japanese population: the Hisayama Study.
    Fujiwara K, Yasuda M, Hata J, Oshima Y, Hashimoto S, Yoshitomi T, Kiyohara Y, Tatsuro Ishibashi, Toshiharu Ninomiya, Koh-Hei Sonoda.
    Seminars in Ophthalmology. 2018;33(6):813-819.
  • Normal foveal and macular thickness measurements using optical coherence tomography in a general Japanese population: the Hisayama Study.
    Hashimoto S, Yasuda M, Ninomiya T, Doi Y, Noda Y, Asakuma T, Hirakawa Y, Kiyohara Y, Ishibashi T.
    Ophthalmic Emidemiol. 2016 Jun;23(3):202-8
  • Insulin resistance is a risk factor for increased intraocular pressure: the Hisayama Study.
    Fujiwara K, Yasuda M, Ninomiya T, Hata J, Hashimoto S, Yoshitomi T, Kiyohara Y, Ishibashi T.
    Invest Ophthalmol Vis Sci. 2015 Dec;56(13):7983-7
  • Thresholds of various glycemic measures for diagnosing diabetes based on prevalence of retinopathy in community-dwelling Japanese subjects: The Hisayama Study.
    Mukai N, Yasuda M, Ninomiya T, Hata J, Hirakawa Y, Ikeda F, Fukuhara M, Hotta T, Koga M, Nakamura U, kang D, Kitazono T, Kiyohara.
    Cardiovascular Diabetology. 2014 Feb;17:13:45
  • Prevalence and risk factors for myopic retinopathy in a Japanese population: the Hisayama Study.
    Asakuma T, Yasuda M, Ninomiya T, Noda Y, Arakawa S, Hashimoto S, Ohno-Matsui K, Kiyohara Y, Ishibashi T.
    Ophthalmology. 2012 Sep;119(9):1760-5
  • Global prevalence and major risk factor of diabetic retinopathy.
    Yau JW, Rogers SL, Kawasaki R, Lamoureux EL, Kowalski JW, Bek T, Chen SJ, Dekker JM, Fletcher A, Grauslund J, Haffner S, Hamman RF, Ikram MK, Kayama T, Klein BE, Klein R, Krishnaiah S, Mayurasakorn K, O'Hare JP, Orchard TJ, Porta M, Rema M, Roy MS, Sharma T, Shaw J, Taylor H, Tielsch JM, Varma R, Wang JJ, Wang N, West S, Xu L, Yasuda M, Zhang X, Mitchell P, Wong TY; Meta-Analysis for Eye Disease (META-EYE) Study Group.
    Diabetes Care. 2012 Mar;35(3):556-64
  • Genome-wide association study identifies two susceptibility loci for exudative age-related macular degeneration in the Japanese population.
    Arakawa S, Takahashi A, Ashikawa K, Hosono N, Aoi T, Yasuda M, Oshima Y, Yoshida S, Enaida H, Tsuchihashi T, Mori K, Honda S, Negi A, Arakawa A, Kadonosono K, Kiyohara Y, Kamatani N, Nakamura Y, Ishibashi T, Kubo M .
    Nat Genet. 2011 Sep 11;43(10):1001-4
  • Nine-year incidence and risk factors for retinal vein occlusion in a general Japanese population: the Hisayama Study.
    Arakawa S, Yasuda M, Nagata M, Ninomiya T, Hirakawa Y, Doi Y, Kiyohara Y, Ishibashi T.
    Invest Ophthalmol Vis Sci. 2011 Jul;52(8):5905-9
  • High serum bilirubin levels and diabetic retinopathy: The Hisayama Study.
    Yasuda M, Kiyohara Y, Hata Y, Arakawa S, Yonemoto K, Doi Y, Iida M, Ishibash T.
    Ophthalmology. 2011 Jul;118(7):1423-8
  • Prevalence and systemic risk factors of retinal vein occlusion in a general Japanese population: The Hisayama Study.
    Yasuda M, Kiyohara Y, Hata Y, Arakawa S, Yonemoto K, Doi Y, Iida M, Ishibash T.
    Invest Ophthalmol Vis Sci. 2010 Jun;51(6):3205-9
  • The prevalence of age-related macular degeneration in Asians: a systematic review and meta-analysis.
    Kawasaki R, Yasuda M, Song SJ, Chen SJ, Jonas JB, Wang JJ, Mitchell P, Wong TY.
    Ophthalmology. 2010 May;117(5):921-7
  • The prevalence and number of people with retinal vein occlusion: Pooled data from population-based studies from the US, Europe, Australia and Asia.
    Rogers S, Mclntosh RL, Cheung N, Lim L, Wang JJ, Paul M , Klein R, Klein BEK, Xu L, JonasJ, Chakravarthy U, Fletcher A, Kawasaki R, Yamashita H, Wang N, Liang Y, Yasuda M, Ishibashi T,Kiyohara Y, Varma R, Cotch MF, West S, Munoz B, Vingerling J, Jong P, Cheng CY, Shen Sj, Saw SM, Aung T, Wong TY.
    Ophthalmology 2010 Feb;117(2):313-9
  • Nine-year incidence and risk factors for age-related macular degeneration in a defined Japanese population: The Hisayama Study.
    Yasuda M, Kiyohara Y, Hata Y, Arakawa S, Yonemoto K, Doi Y, Iida M, Ishibash T.
    Ophthalmology. 2009 Nov;116(11):2135-40
  • The prevalence of pseudoexfoliation syndrome in a Japanese population: The Hisayama Study.
    Miyazaki M, Kubota T, Kubo M, Kiyohara Y, Iida M, Nose Y, Ishibash T.
    J glaucoma. 2005 Dec;14(6):482-4
  • The five-year incidence and risk factors for age related maculopathy in a general Japanese population: the Hisayama Study.
    Miyazaki M, Kiyohara Y, Yoshida A, Iida M, Nose Y, Ishibash T.
    Invest Ophthalmol Vis Sci. 2005 Jun;46(6):1907-10
  • Comparison of diagnostic methods for diabetes mellitus based on prevalence of retinopathy in a Japanese population: The Hisayama Study.
    Miyazaki M, Kubo M, Kiyohara Y, Okubo K, Nakamura H, Fujisawa K, Tokunaga S, Iida M, Nose Y, Ishibashi T,
    Diabetologia. 2004 Aug;47(8):1411-5
  • Prevalence and Risk Factors for Epiretinal Membrane in a Japanese Population: the Hisayama Study.
    Miyazaki M, Nakamura H, Kubo M, Kiyohara Y, Iida M, Ishibashi T, Nosa Y.
    Graefe Arch Clin Exp Ophthalmol. 2003 Aug;241(8):642-6
  • Risk Factors for Age-Related Maculopathy in a Japanese Population.
    Miyazaki M, Nakamura H, Kubo M, Kiyohara Y, Oshima Y, Ishibashi T, Nose Y.
    Br J Ophthalmol. 2003 Apr;87(4):469-72

Nerve Regeneration Group

P.I. Koh-Hei Sonoda, Yusuke Murakami, Mitsuru Arima

It is a dream of an ophthalmologist to regenerate photoreceptor cells damaged by retinal diseases such as retinal detachment and diabetic retinopathy.
In recent years retinal regenerative medicine using iPS cells has attracted much attention, but we aim to develop retinal regeneration therapy by direct reprogramming, i.e. nerve regeneration therapy not dependent on cell transplantation. The strategy of future retinal regeneration therapy that we consider is to perform radical therapy for the causative disease and retinal regeneration therapy at the same time by injection of medicine into the vitreous at the end of surgery.
We have already developed a method to change astrocytes and Müller cells into progenitor cells by stimulation with a cocktail of small molecular compounds under in vitro environment and then induce differentiation into neurons. Now we are conducting comprehensive compound screening to select the combination of cocktails that lead to more efficient differentiation into neuronal cells.
Young researchers interested in our research, please contact us at any time!

Selected publications

  • Changes in metabolic proteins in ex vivo rat retina during glutamate-induced neural progenitor cell induction.
    Tokuda K, Kuramitsu Y, Baron B, Kitagawa T, Tokuda N, Kobayashi M, Kimura K, Sonoda KH, Nakamura K.
    Mol Cell Biochem. 2016 Aug;419(1-2):177-84.
  • Up-regulation of DRP-3 long isoform during the induction of neural progenitor cells by glutamate treatment in the ex vivo rat retina.
    Tokuda K, Kuramitsu Y, Byron B, Kitagawa T, Tokuda N, Kobayashi D, Nagayama M, Araki N, Sonoda KH, Nakamura K.
    Biochem Biophys Res Commun. 2015 Aug 7;463(4):593-9.