Department of Ophthalmology,

Kurume University School of Medicine

Address : 67 Asahi-machi,Kurume,Fukuoka 830-0011, Japan

Phone     : 0942-31-7574(+81-942-317574)

Fax         : 0942-37-0324(+81-942-370324)

E-mail  : kurumeye@med.kurume-u.ac.jp

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Message from the Chairman:Bringing light to all

​アクセス

Welcome to the Department of Ophthalmology at Kurume University School of Medicine. I have been leading this department since April 2018. Our department is one of prestigious departments of ophthalmology with a history of 90 years, and has produced many excellent, compassionate physicians and outstanding medical research scientists.

 

The mission of Kurume University is “To search truth and justice, to aim for human love and respect, to foster people who will have practical knowledge, noble ideas and a deep sense of humanity, to brighten the regional culture and show its brilliant results to the world, and to contribute to the peace of the world.” Fostering humanism underlies the mission of Kurume University. It’s my great pleasure to have an opportunity to foster future generations in this university. The core value of our department is to serve humanity. Our dedicated faculty and staff provide comprehensive education to medical students and compassionate care to patients with eye diseases. In rapidly changing medical environment, serving humanity is an eternal value in the past, present, and future. It will remain the core value of the Department of Ophthalmology at Kurume University in 100 years from now.

In ten years our department will mark the 100th anniversary. We will strive to bring hope to future generations by nurturing dream and ambition of young physicians, to bring light to patients suffering from vision threatening diseases, and to contribute to local community.

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Shigeo Yoshida, MD, PhD

Professor and Chairman

Department of Ophthalmology,

Kurume University School of Medicine

・Japanese Ophthalmological Society

・Japanese Society of Diabetic Complications 

・Japanese Society of Opthalmic Diabetology 

・The Retina Society Active Member

・Current Eye Research Editorial board

・Ophthalmic Research Editorial board​

 

Research Focus

1. Development of molecular-targeting therapies for intraocular proliferative 
diseases including Diabetic retinopathy 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 intraocular proliferation.


As mentioned above, we have identified approximately a hundred key molecules that are highly expressed in PDR- and in PVR-ERMs (Ishikawa K et al. IOVS 2015). 
We can explore the underlying disease mechanisms associated with PDR and/or AMD.
Check the expression and distribution of the molecule in the animal models of both retinal and choroidal neovascularization (OIR and CNV) by real-time PCR, ELISA, Western blot and IHC, etc (Figure 3).
Kyushu University has very large operation number, so human samples or clinical information can be obtained. The expression of those key molecules can thus be determined using those surgically-resected ERMs and vitreous samples. 
The interaction of those key molecules can be determined with other important factors, such as VEGF, periostin, tenascin C, and macrophages.
The pathways mediated by those molecules can be further examined by in an vitro assay.
Check the inhibitory effect of those molecules in both animal models, and determine whether the molecules can be additional new therapeutic targets.

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Selected Publications

1    S. Yoshida, M. Ono, T. Shono, H. Izumi, T. Ishibashi, H. Suzuki, and M. Kuwano, 'Involvement of Interleukin-8, Vascular Endothelial Growth Factor, and Basic Fibroblast Growth Factor in Tumor Necrosis Factor Alpha-Dependent Angiogenesis', Mol Cell Biol, 17 (1997), 4015-23.
2    S. Yoshida, Y. Kumano, A. Yoshida, S. Numa, N. Yabe, T. Hisatomi, T. Nishida, T. Ishibashi, and T. Matsui, 'Two Brothers with Gelatinous Drop-Like Dystrophy at Different Stages of the Disease: Role of Mutational Analysis', Am J Ophthalmol, 133 (2002), 830-2.
3    S. Yoshida, A. Yoshida, T. Ishibashi, S. G. Elner, and V. M. Elner, 'Role of Mcp-1 and Mip-1alpha in Retinal Neovascularization During Postischemic Inflammation in a Mouse Model of Retinal Neovascularization', J Leukoc Biol, 73 (2003), 137-44.
4    S. Yoshida, R. Arita, A. Yoshida, H. Tada, A. Emori, Y. Noda, S. Nakao, K. Fujisawa, and T. Ishibashi, 'Novel Mutation in Fzd4 Gene in a Japanese Pedigree with Familial Exudative Vitreoretinopathy', Am J Ophthalmol, 138 (2004), 670-1.
5    S. Yoshida, H. Yoshikawa, A. Yoshida, T. Nakamura, Y. Noda, H. Gondoh, S. Fukagawa, Y. Moroi, K. Urabe, M. Furue, and T. Ishibashi, 'Bilateral Epiretinal Membranes in Nevoid Basal Cell Carcinoma Syndrome', Acta Ophthalmol Scand, 82 (2004), 488-90.
6    S. Yoshida, A. Yoshida, and T. Ishibashi, 'Induction of Il-8, Mcp-1, and Bfgf by Tnf-Alpha in Retinal Glial Cells: Implications for Retinal Neovascularization During Post-Ischemic Inflammation', Graefes Arch Clin Exp Ophthalmol, 242 (2004), 409-13.
7    S. Yoshida, A. Yoshida, S. Nakao, A. Emori, T. Nakamura, K. Fujisawa, Y. Kumano, and T. Ishibashi, 'Lattice Corneal Dystrophy Type I without Typical Lattice Lines: Role of Mutational Analysis', Am J Ophthalmol, 137 (2004), 586-8.
8    K. Yoshimura, S. Yoshida, Y. Yamaji, A. Komori, A. Yoshida, K. Hatae, T. Kubota, and T. Ishibashi, 'De Novo Insg619 Mutation in Pax2 Gene in a Japanese Patient with Papillorenal Syndrome', Am J Ophthalmol, 139 (2005), 733-5.
9    S. Yoshida, Y. Yamaji, A. Yoshida, Y. Noda, Y. Kumano, and T. Ishibashi, 'Rapid Genotyping for Most Common Tgfbi Mutations with Real-Time Polymerase Chain Reaction', Hum Genet, 116 (2005), 518-24.
10    S. Yoshida, M. Honda, A. Yoshida, S. Nakao, Y. Goto, T. Nakamura, K. Fujisawa, and T. Ishibashi, 'Novel Mutation in Abcc6 Gene in a Japanese Pedigree with Pseudoxanthoma Elasticum and Retinitis Pigmentosa', Eye (Lond), 19 (2005), 215-7.
11    S. Yoshida, Y. Yamaji, A. Yoshida, R. Kuwahara, K. Yamamoto, T. Kubata, and T. Ishibashi, 'Novel Triple Missense Mutations of Gucy2d Gene in Japanese Family with Cone-Rod Dystrophy: Possible Use of Genotyping Microarray', Mol Vis, 12 (2006), 1558-64.
12    S. Yoshida, Y. Yamaji, A. Yoshida, Y. Ikeda, K. Yamamoto, and T. Ishibashi, 'Rapid Detection of Sag 926dela Mutation Using Real-Time Polymerase Chain Reaction', Mol Vis, 12 (2006), 1552-7.
13    S. Yoshida, Y. Yamaji, A. Yoshida, R. Kuwahara, K. Fujisawa, and T. Ishibashi, 'Prognostic DNA Testing and Counselling for Dominant Optic Atrophy Due to a Novel Opa1 Mutation', Can J Ophthalmol, 41 (2006), 614-6.
14    S. Yoshida, Y. Yamaji, R. Kuwahara, A. Yoshida, T. Hisatomi, A. Ueno, and T. Ishibashi, 'Novel Mutation in Exon 2 of Col2a1 Gene in Japanese Family with Stickler Syndrome Type I', Eye (Lond), 20 (2006), 743-5.
15    Y. Yamaji, S. Yoshida, K. Ishikawa, A. Sengoku, K. Sato, A. Yoshida, R. Kuwahara, K. Ohuchida, E. Oki, H. Enaida, K. Fujisawa, T. Kono, and T. Ishibashi, 'Tem7 (Plxdc1) in Neovascular Endothelial Cells of Fibrovascular Membranes from Patients with Proliferative Diabetic Retinopathy', Invest Ophthalmol Vis Sci, 49 (2008), 3151-7.
16    S. Yoshida, K. Ishikawa, T. Matsumoto, A. Yoshida, T. Ishibashi, and T. Kono, 'Reduced Concentrations of Angiogenesis-Related Factors in Vitreous after Vitrectomy in Patients with Proliferative Diabetic Retinopathy', Graefes Arch Clin Exp Ophthalmol, 248 (2010), 799-804.
17    S. Yoshida, A. Ogura, K. Ishikawa, A. Yoshida, R. Kohno, Y. Yamaji, K. Ikeo, T. Gojobori, T. Kono, and T. Ishibashi, 'Gene Expression Profile of Fibrovascular Membranes from Patients with Proliferative Diabetic Retinopathy', Br J Ophthalmol, 94 (2010), 795-801.
18    S. Yoshida, K. Ishikawa, R. Asato, M. Arima, Y. Sassa, A. Yoshida, H. Yoshikawa, K. Narukawa, S. Obika, J. Ono, S. Ohta, K. Izuhara, T. Kono, and T. Ishibashi, 'Increased Expression of Periostin in Vitreous and Fibrovascular Membranes Obtained from Patients with Proliferative Diabetic Retinopathy', Invest Ophthalmol Vis Sci, 52 (2011), 5670-8.
19    S. Yoshida, T. Nakama, K. Ishikawa, M. Arima, T. Tachibana, S. Nakao, Y. Sassa, M. Yasuda, H. Enaida, Y. Oshima, T. Kono, and T. Ishibashi, 'Antiangiogenic Shift in Vitreous after Vitrectomy in Patients with Proliferative Diabetic Retinopathy', Invest Ophthalmol Vis Sci, 53 (2012), 6997-7003.
20    R. Asato, S. Yoshida, A. Ogura, T. Nakama, K. Ishikawa, S. Nakao, Y. Sassa, H. Enaida, Y. Oshima, K. Ikeo, T. Gojobori, T. Kono, and T. Ishibashi, 'Comparison of Gene Expression Profile of Epiretinal Membranes Obtained from Eyes with Proliferative Vitreoretinopathy to That of Secondary Epiretinal Membranes', PLoS One, 8 (2013), e54191.
21    K. Ishikawa, S. Yoshida, S. Nakao, T. Nakama, T. Kita, R. Asato, Y. Sassa, R. Arita, M. Miyazaki, H. Enaida, Y. Oshima, N. Murakami, H. Niiro, J. Ono, A. Matsuda, Y. Goto, K. Akashi, K. Izuhara, A. Kudo, T. Kono, A. Hafezi-Moghadam, and T. Ishibashi, 'Periostin Promotes the Generation of Fibrous Membranes in Proliferative Vitreoretinopathy', FASEB J, 28 (2014), 131-42.
22    Y. Zhou, S. Yoshida, S. Nakao, T. Yoshimura, Y. Kobayashi, T. Nakama, Y. Kubo, K. Miyawaki, M. Yamaguchi, K. Ishikawa, Y. Oshima, K. Akashi, and T. Ishibashi, 'M2 Macrophages Enhance Pathological Neovascularization in the Mouse Model of Oxygen-Induced Retinopathy', Invest Ophthalmol Vis Sci, 56 (2015), 4767-77.
23    T. Tachibana, S. Yoshida, Y. Kobayashi, T. Nakama, K. Ishikawa, A. Sengoku, S. Nakao, Y. Oshima, and T. Ishibashi, 'Differential Improvement of Vertical and Horizontal Metamorphopsia Scores after Epiretinal Membrane Vitrectomy with Ilm Peeling', Acta Ophthalmol, 93 (2015), e681-2.
24    S. Yoshida, Y. Kubo, Y. Kobayashi, Y. Zhou, T. Nakama, M. Yamaguchi, T. Tachibana, K. Ishikawa, R. Arita, S. Nakao, Y. Sassa, Y. Oshima, T. Kono, and T. Ishibashi, 'Increased Vitreous Concentrations of Mcp-1 and Il-6 after Vitrectomy in Patients with Proliferative Diabetic Retinopathy: Possible Association with Postoperative Macular Oedema', Br J Ophthalmol, 99 (2015), 960-6.
25    K. Ishikawa, S. Yoshida, Y. Kobayashi, Y. Zhou, T. Nakama, S. Nakao, Y. Sassa, Y. Oshima, H. Niiro, K. Akashi, T. Kono, and T. Ishibashi, 'Microarray Analysis of Gene Expression in Fibrovascular Membranes Excised from Patients with Proliferative Diabetic Retinopathy', Invest Ophthalmol Vis Sci, 56 (2015), 932-46.
26    T. Nakama, S. Yoshida, K. Ishikawa, Y. Kobayashi, Y. Zhou, S. Nakao, Y. Sassa, Y. Oshima, K. Takao, A. Shimahara, K. Yoshikawa, T. Hamasaki, T. Ohgi, H. Hayashi, A. Matsuda, A. Kudo, M. Nozaki, Y. Ogura, M. Kuroda, and T. Ishibashi, 'Inhibition of Choroidal Fibrovascular Membrane Formation by New Class of Rna Interference Therapeutic Agent Targeting Periostin', Gene Ther, 22 (2015), 127-37.
27    S. Yoshida, Y. Kobayashi, T. Nakama, Y. Zhou, K. Ishikawa, R. Arita, S. Nakao, M. Miyazaki, Y. Sassa, Y. Oshima, K. Izuhara, T. Kono, and T. Ishibashi, 'Increased Expression of M-Csf and Il-13 in Vitreous of Patients with Proliferative Diabetic Retinopathy: Implications for M2 Macrophage-Involving Fibrovascular Membrane Formation', Br J Ophthalmol, 99 (2015), 629-34.
28    Y. Kobayashi, S. Yoshida, T. Nakama, Y. Zhou, K. Ishikawa, R. Arita, S. Nakao, M. Miyazaki, Y. Sassa, Y. Oshima, K. Izuhara, T. Kono, and T. Ishibashi, 'Overexpression of Cd163 in Vitreous and Fibrovascular Membranes of Patients with Proliferative Diabetic Retinopathy: Possible Involvement of Periostin', Br J Ophthalmol, 99 (2015), 451-6.
29    T. Nakama, S. Yoshida, K. Ishikawa, Y. Kobayashi, T. Abe, H. Kiyonari, G. Shioi, N. Katsuragi, T. Ishibashi, R. Morishita, and Y. Taniyama, 'Different Roles Played by Periostin Splice Variants in Retinal Neovascularization', Exp Eye Res, 153 (2016), 133-40.
30    Y. Kobayashi, S. Yoshida, Y. Zhou, T. Nakama, K. Ishikawa, Y. Kubo, M. Arima, S. Nakao, T. Hisatomi, Y. Ikeda, A. Matsuda, K. H. Sonoda, and T. Ishibashi, 'Tenascin-C Secreted by Transdifferentiated Retinal Pigment Epithelial Cells Promotes Choroidal Neovascularization Via Integrin Alphav', Lab Invest, 96 (2016), 1178-88.
31    Y. Koyanagi, S. Yoshida, Y. Kobayashi, Y. Kubo, M. Yamaguchi, T. Nakama, S. Nakao, Y. Ikeda, Y. Ohshima, T. Ishibashi, and K. H. Sonoda, 'Comparison of the Effectiveness of Intravitreal Ranibizumab for Diabetic Macular Edema in Vitrectomized and Nonvitrectomized Eyes', Ophthalmologica, 236 (2016), 67-73.
32    Y. Zhou, S. Yoshida, Y. Kubo, Y. Kobayashi, T. Nakama, M. Yamaguchi, K. Ishikawa, S. Nakao, Y. Ikeda, T. Ishibashi, and K. H. Sonoda, 'Interleukin-12 Inhibits Pathological Neovascularization in Mouse Model of Oxygen-Induced Retinopathy', Sci Rep, 6 (2016), 28140.
33    Y. Kobayashi, S. Yoshida, Y. Zhou, T. Nakama, K. Ishikawa, M. Arima, S. Nakao, Y. Sassa, A. Takeda, T. Hisatomi, Y. Ikeda, A. Matsuda, K. H. Sonoda, and T. Ishibashi, 'Tenascin-C Promotes Angiogenesis in Fibrovascular Membranes in Eyes with Proliferative Diabetic Retinopathy', Mol Vis, 22 (2016), 436-45.
34    Y. Sassa, S. Yoshida, K. Ishikawa, R. Asato, T. Ishibashi, and T. Kono, 'The Kinetics of Vegf and Mcp-1 in the Second Vitrectomy Cases with Proliferative Diabetic Retinopathy', Eye (Lond), 30 (2016), 746-53.
35    T. Tachibana, S. Yoshida, Y. Kubo, Y. Koayashi, T. Nakama, K. Ishikawa, S. Nakao, K. Izuhara, T. Kono, and T. Ishibashi, 'Reduced Vitreal Concentration of Periostin after Vitrectomy in Patients with Proliferative Diabetic Retinopathy', Acta Ophthalmol, 94 (2016), e81-2.
36    I. Wada, S. Yoshida, Y. Kobayashi, Y. Zhou, K. Ishikawa, S. Nakao, T. Hisatomi, Y. Ikeda, T. Ishibashi, and K. H. Sonoda, 'Quantifying Metamorphopsia with M-Charts in Patients with Idiopathic Macular Hole', Clin Ophthalmol, 11 (2017), 1719-26.
37    S. Yoshida, Y. Kobayashi, S. Nakao, Y. Sassa, T. Hisatomi, Y. Ikeda, Y. Oshima, T. Kono, T. Ishibashi, and K. H. Sonoda, 'Differential Association of Elevated Inflammatory Cytokines with Postoperative Fibrous Proliferation and Neovascularization after Unsuccessful Vitrectomy in Eyes with Proliferative Diabetic Retinopathy', Clin Ophthalmol, 11 (2017), 1697-705.
38    M. Berdasco, A. Gomez, M. J. Rubio, J. Catala-Mora, V. Zanon-Moreno, M. Lopez, C. Hernandez, S. Yoshida, T. Nakama, K. Ishikawa, T. Ishibashi, A. M. Boubekeur, L. Louhibi, M. A. Pujana, S. Sayols, F. Setien, D. Corella, C. de Torres, A. Parareda, J. Mora, L. Zhao, K. Zhang, M. E. Lleonart, J. Alonso, R. Simo, J. M. Caminal, and M. Esteller, 'DNA Methylomes Reveal Biological Networks Involved in Human Eye Development, Functions and Associated Disorders', Sci Rep, 7 (2017), 11762.
39    S. Yoshida, T. Nakama, K. Ishikawa, S. Nakao, K. H. Sonoda, and T. Ishibashi, 'Periostin in Vitreoretinal Diseases', Cell Mol Life Sci, 74 (2017), 4329-37.
40    S. Yoshida, S. Yamana, R. Inoue, Y. Kubo, Y. Kobayashi, T. Nakama, K. H. Sonoda, and T. Ishibashi, 'A Case of Diabetic Macular Edema with Improvement in Severity of Diabetic Retinopathy Following Frequent Anti-Vascular Endothelial Growth Factor Treatment', Nippon Ganka Gakkai Zasshi, 121 (2017), 425-30.
41    Y. Zhou, S. Yoshida, Y. Kubo, T. Yoshimura, Y. Kobayashi, T. Nakama, M. Yamaguchi, K. Ishikawa, Y. Oshima, and T. Ishibashi, 'Different Distributions of M1 and M2 Macrophages in a Mouse Model of Laser-Induced Choroidal Neovascularization', Mol Med Rep, 15 (2017), 3949-56.
42    T. Nakama, S. Yoshida, K. Ishikawa, Y. Kubo, Y. Kobayashi, Y. Zhou, S. Nakao, T. Hisatomi, Y. Ikeda, K. Takao, K. Yoshikawa, A. Matsuda, J. Ono, S. Ohta, K. Izuhara, A. Kudo, K. H. Sonoda, and T. Ishibashi, 'Therapeutic Effect of Novel Single-Stranded Rnai Agent Targeting Periostin in Eyes with Retinal Neovascularization', Mol Ther Nucleic Acids, 6 (2017), 279-89.
43    T. Hisatomi, T. Tachibana, S. Notomi, S. Nakatake, K. Fujiwara, Y. Murakami, Y. Ikeda, S. Yoshida, H. Enaida, T. Murata, T. Sakamoto, K. H. Sonoda, and T. Ishibashi, 'Incomplete Repair of Retinal Structure after Vitrectomy with Internal Limiting Membrane Peeling', Retina, 37 (2017), 1523-28.