Ocular Inflammation Group

Elucidation of pathogenesis of uveitis and development of diagnostics and optimized therapeutics by analyzing clinical specimens

P.I.;Koh-Hei Sonoda , Nobuyo Yawata

Uveitis is a diverse group of diseases, including infectious, autoimmune, autoinflammatory, and malignant diseases, with large variations. Different responses to treatment and prognoses call attention to the importance of human immunology research and the elucidation of diverse disease pathologies. In recent years, advanced technologies such as single-cell analysis and next-generation sequencing (NGS) have developed, which enable us to obtain a great extent of information from a limited amount of clinical specimens. They are powerful tools in elucidating the pathogenesis and stratification of inflammatory diseases. In order to clarify the factors involved in ocular inflammation and treatment responsiveness, and to develop diagnostic techniques and optimal therapeutics, our laboratory is analyzing intraocular fluid and blood specimens of uveitis at the gene expression, protein, and cellular levels using these state-of-the-art technologies.
We are also collaborating with uveitis treatment specialists and research institutions across the country to advance our research.

Elucidation of pathogenesis of autoimmune uveitis.

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). We recently elucidated that mucosal-associated invariant T (MAIT) cells (Yamana S et al. Mucosal Immunol. 2022) are related to the pathogenesis of uveitis. MAIT cells are an innate-like T cell subset that harbors unique invariant TRAV1-TRAJ33+ chains paired with limited T cell receptor (TCR) β chains. An EAU experiment revealed that genetic depletion of MAIT cells exacerbated retinal pathology. An intravitreal administration of an antigenic metabolite of MAIT cells into EAU mice induced retinal MAIT cell expansion, leading to an improvement in retinal pathology. Further research is currently underway to develop novel therapies for uveitis targeting MAIT cells.

Selected publications

1. A multicenter study of ocular inflammation after COVID-19 vaccination.
   Yasaka Y, Hasegawa E, Keino H, Usui Y, Maruyama K, Yamamoto Y, Kaburaki T, Iwata D, Takeuchi M, Kusuhara S, Takase H, Nagata K, Yanai R, Kaneko Y, Iwahashi C, Fukushima A, Ohguro N, Sonoda KH; JOIS Uveitis Survey Working Group. Jpn J Ophthalmol. 2023 Jan;67(1):14-21. doi: 10.1007/s10384-022-00962-9.
2. Intraocular human cytomegaloviruses of ocular diseases are distinct from those of viremia and are capable of escaping from innate and adaptive immunity by exploiting HLA-E-mediated peripheral and central tolerance.
   Shirane M, Yawata N, Motooka D, Shibata K, Khor SS, Omae Y, Kaburaki T, Yanai R, Mashimo H, Yamana S, Ito T, Hayashida A, Mori Y, Numata A, Murakami Y, Fujiwara K, Ohguro N, Hosogai M, Akiyama M, Hasegawa E, Paley M, Takeda A, Maenaka K, Akashi K, Yokoyama WM, Tokunaga K, Yawata M, Sonoda KH. Front Immunol. 2022 Oct 19; 13:1008220. doi: 10.3389/fimmu.2022.1008220.
3. Factors associated with low prevalence of Fuchs' uveitis syndrome in Japan.
   Yoneda Y, Usui Y, Tanaka R, Hase K, Namba K, Kamoi K, Takase H, Takeuchi M, Matsumiya W, Kusuhara S, Takeda A, Yawata N, Yanai R, Hiyama T, Harada Y, Hashida N, Maruyama K, Nakai K, Taguchi R, Kaburaki T, Mizuki N, Goto H, Fujino Y, Takeuchi M. Front Med (Lausanne). 2022 Sep 30; 9:999804. doi: 10.3389/fmed.2022.999804.
4. Long-term outcomes of infliximab in patients with Behçet's disease-associated uveitis.
   Yamana S, Hasegawa E, Takeda A, Yawata N, Sonoda KH. Int Ophthalmol. 2022 Sep 4. doi: 10.1007/s10792-022-02495-z. Online ahead of print.
5. Pauveitis induced by donor-derived CD8+ T cells after allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia.
   Takeda A, Sakoda T, Yawata N, Kato K, Hasegawa E, Shima T, Hikita S, Yoshitomi K, Takenaka K, Oda Y, Akashi K, Sonoda KH. Am J Ophthalmol Case Rep. 2022 Aug 5; 27:101673. doi:
   10.1016/j.ajoc.2022.101673.
6. Increased vitreous levels of B cell activation factor (BAFF) and soluble interleukin-6 receptor in patients with macular edema due to uveitis related to Behçet's disease and sarcoidosis.
   Takeda A, Hasegawa E, Yawata N, Notomi S, Ishikawa K, Murakami Y, Hisatomi T, Kimura K, Sonoda KH.
   Graefes Arch Clin Exp Ophthalmol. 2022 Mar 1. doi: 10.1007/s00417-022-05600-1.
7. Mucosal-associated invariant T cells have therapeutic potential against ocular autoimmunity.
   Yamana S, Shibata K, Hasegawa E, Arima M, Shimokawa S, Yawata N, Takeda A, Yamasaki S, Sonoda KH.
   Mucosal Immunol. 2022 Feb;15(2):351-361. doi: 10.1038/s41385-021-00469-5.
8. Takeda A, Hasegawa E, Notomi S, Ishikawa K, Arima M, Murakami Y, Nakao S, Hisatomi T, Sonoda KH. Clin Ophthalmol. 2021 Jun 24; 15:2665-2673. doi: 10.2147/OPTH.S314173.
9. Molecular Signatures of Natural Killer Cells in CMV-Associated Anterior Uveitis, A New Type of CMV-Induced Disease in Immunocompetent Individuals.
   Yawata N, Shirane M, Woon K, Lim X, Tanaka H, Kawano YI, Yawata M, Chee SP, Siak J, Sonoda KH. Int J Mol Sci. 2021 Mar 31;22(7):3623. doi: 10.3390/ijms22073623.
10. Epidemiology of uveitis in Japan: a 2016 retrospective nationwide survey. Sonoda KH, Hasegawa E, Namba K, Okada AA, Ohguro N, Goto H; JOIS (Japanese Ocular Inflammation Society) Uveitis Survey Working Group. Jpn J Ophthalmol. 2021 Mar;65(2):184-190. doi: 10.1007/s10384-020-00809-1.
11. Vitreous levels of interleukin-35 as a prognostic factor in B-cell vitreoretinal lymphoma.
    Takeda A, Hasegawa E, Nakao S, Ishikawa K, Murakami Y, Hisatomi T, Arima M, Yawata N, Oda Y, Kimura K, Yoshikawa H, Sonoda KH.
    Sci Rep. 2020 Sep 24;10(1):15715. doi: 10.1038/s41598-020-72962-z.
12. New insights into immunological therapy for retinal disorders.
    Takeda A, Yanai R, Murakami Y, Arima M, Sonoda KH.
    Front Immunol. 2020 Jul 3;11:1431. doi: 10.3389/fimmu.2020.01431. eCollection 2020.
13. Risk factors for failure of vitrectomy cell block technique in cytological diagnosis of vitreoretinal lymphoma.
    Ito T, Takeda A, Fujiwara K, Hasegawa E, Nakao S, Ohishi Y, Oda Y, Yoshikawa H, Sonoda KH.
    Graefes Arch Clin Exp Ophthalmol. 2019 May;257(5):1029-1036. doi: 10.1007/s00417-019-04266-6.
14. The effectiveness of adalimumab treatment for non-infectious uveitis.
    Hasegawa E, Takeda A, Yawata N, Sonoda KH.
    Immunol Med. 2019 Jun;42(2):79-83. doi: 10.1080/25785826.2019.1642080.
15. Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model.
    Sato K, Takeda A, Hasegawa E, Jo YJ, Arima M, Oshima Y, Ryoji Y, Nakazawa T, Yuzawa M, Nakashizuka H, Shimada H, Kimura K, Ishibashi T, Sonoda KH.
    Immunol Med. 2018 Mar;41(1):23-29. doi: 10.1080/09114300.2018.1451609.
16. 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.
17. 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.
18. 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. Review.