Can we prevent silicone-oil related vision loss perfectly?

• Project/Area Number: 19K09988
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Nagoya University
• Principal Investigator: Kaneko Hiroki 名古屋大学, 医学部附属病院, 講師 (20647458)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: シリコーンオイル / 炎症性サイトカイン / 電解質 / 光障害 / 網膜フェロトーシス / シリコーンオイル下液 / FeRhoNox-1 / 鉄 / iron / 4-HNE / 網膜 / サイトカイン / 酸素飽和度

Outline of Research at the Start

近年になり原因不明のSO関連視力低下(SORVL)という概念が再浮上した。私はSORVLの原因として①SO下液中の高濃度炎症性サイトカインによる網膜毒性、②SO下液中の電解質異常、③SO充填眼に照射される顕微鏡光による光障害、④SO充填眼の網膜酸素飽和度異常、のいずれかが関与していると仮説を立てた。本研究では、SO下液のサイトカイン・電解質測定やSO充填眼におけるSO充填率と光の集光、SO抜去眼の網膜血管変化などを科学的に検証し、SORVLの本当の原因を明らかにするとともに、その解決策を学会等で広く報告し、医師・患者双方にとって不幸なSORVLを未然に防ぎたい。

Outline of Final Research Achievements

Silicone oil (SO) has been used as a surgical adjuvant in vitreoretinal surgery for a long time, and the merits and demerits of its use have been thoroughly investigated in the past, but the concept of SO-related vision loss of unknown origin (SORVL) has recently resurfaced. I hypothesized that SORVL is caused by one of the following: (1) retinal toxicity due to high concentrations of inflammatory cytokines in the sub-SO fluid, (2) electrolyte abnormalities in the sub-SO fluid, (3) phototoxicity due to microscopic light irradiating the SO-filled eye, or (4) abnormal retinal oxygen saturation in the SO-filled eye. In the present study, we confirmed that only Fe (iron) was significantly decreased in electrolytes in the sub-SO fluid. Furthermore, we succeeded in confirming the scientific evidence that the retina intakes Fe from the vitreous humor and undergoes Fe-related cell death (ferroptosis) using cultured cells, experimental animals, and human specimens.

Academic Significance and Societal Importance of the Research Achievements

本研究課題では、SOに伴う原因不明の視力低下(SORVL)症例に対し、その原因を科学的に検証した。この科学現象が起きる条件を今後発見できれば、SORVLを発生させない新規素材の開発や手術室での環境変更を提唱することでSORVLという現象を防ぐことが可能となる。残る課題としてSOの酸素透過性が非常に硬いことによる網膜への影響を分析することが挙げられ、これには現存するOxymap等の機械を使用することが計画される。さらに、網膜がSO自体を「異物」と誤認することによってフェロトーシスが生じている可能性も十分考えられ、SOだけでなく感染性疾患における網膜障害の治療につながる可能性も残っている。

Research Products

• [Journal Article] Seasonal variation in submacular hemorrhages in retinal macroaneurysms and its disappearance in age-related macular degeneration. (2021)
  • Author(s): Kaneko H, Takashi N, Matsunaga M, Ito Y, Takeuchi J, Terasaki H, Yatsuya H, Nishiguchi KM.
  • Journal Title: Graefes Arch Clin Exp Ophthalmol. Volume: 259 Pages: 3589-3596
  • Peer Reviewed
• [Journal Article] Optical coherence tomography angiography for the diagnosis of granulomatosis with polyangiitis with serous retinal detachment: A case report. (2021)
  • Author(s): Takashi N, Nakamura A, Kataoka K, Usui Y, Ito Y, Kaneko H*
  • Journal Title: Medicine (Baltimore) Volume: 100
  • Peer Reviewed / Open Access
• [Journal Article] Intra- and Postoperative Monitoring of Autologous Neurosensory Retinal Flap Transplantation for Refractory Macular Hole Associated with High Myopia (2020)
  • Author(s): Takeuchi J, Kataoka K, Shimizu H, Tomita R, Kominami T, Ushida H, Kaneko H, Ito Y, Terasaki H.
  • Journal Title: Retina Volume: - Issue: 5 Pages: 921-930
  • DOI: 10.1097/iae.0000000000003000
  • Peer Reviewed / Open Access
• [Journal Article] Effect of internal limiting membrane peeling on visual field sensitivity in eyes with epiretinal membrane accompanied by glaucoma with hemifield defect and myopia (2020)
  • Author(s): Kaneko H*, Hirata N, Shimizu H, Kataoka K, Nonobe N, Mokuno K, Terasaki H
  • Journal Title: Jpn J Ophthalmol Volume: - Issue: 3 Pages: 380-387
  • DOI: 10.1007/s10384-021-00817-9
  • NAID: 40022562044
  • Peer Reviewed / Open Access
• [Journal Article] n-3 Fatty Acid and Its Metabolite 18-HEPE Ameliorate Retinal Neuronal Cell Dysfunction by Enhancing M?ller BDNF in Diabetic Retinopathy (2020)
  • Author(s): Suzumura Ayana、Kaneko Hiroki、Funahashi Yasuhito、Takayama Kei、Nagaya Masatoshi、Ito Seina、Okuno Toshiaki、Hirakata Toshiaki、Nonobe Norie、Kataoka Keiko、Shimizu Hideyuki、Namba Rina、Yamada Kazuhisa、Ye Fuxiang、Ozawa Yoko、Yokomizo Takehiko、Terasaki Hiroko
  • Journal Title: Diabetes Volume: 69 Issue: 4 Pages: 724-735
  • DOI: 10.2337/db19-0550
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Diacron reactive oxygen metabolites and biological antioxidant potential tests for patients with age-related macular degeneration (2020)
  • Author(s): Matsuura T, Kaneko H*, Takayama K, Shibata R, Kataoka K, Ito S, Tsunekawa T, Shimizu H, Suzumura A, Namba R, Ito Y, Murohara T, Terasaki H.
  • Journal Title: BMC Ophthalmol Volume: 20 Issue: 1 Pages: 56-56
  • DOI: 10.1186/s12886-020-01334-y
  • Peer Reviewed / Open Access
• [Journal Article] Lipid Signaling in Ocular Neovascularization (2020)
  • Author(s): Terao R, Kaneko H.
  • Journal Title: Int J Mol Sci. Volume: 21 Issue: 13 Pages: 4758-4758
  • DOI: 10.3390/ijms21134758
  • Peer Reviewed / Open Access
• [Journal Article] Lamivudine Inhibits Alu RNA-induced Retinal Pigment Epithelium Degeneration via Anti-inflammatory and Anti-senescence Activities (2020)
  • Author(s): Yamada K, Kaneko H*, Shimizu H, Suzumura A, Namba R, Takayama K, Ito S, Sugimoto M, Terasaki H.
  • Journal Title: Transl Vis Sci Technol. Volume: 9 Issue: 8 Pages: 1-1
  • DOI: 10.1167/tvst.9.8.1
  • Peer Reviewed / Open Access
• [Journal Article] Caveolin-1 Promotes Cellular Senescence in Exchange for Blocking Subretinal Fibrosis in Age-Related Macular Degeneration (2020)
  • Author(s): Shimizu H, Yamada K, Suzumura A, Kataoka K, Takayama K, Sugimoto M, Terasaki H, Kaneko H
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 61 Issue: 11 Pages: 21-21
  • DOI: 10.1167/iovs.61.11.21
  • Peer Reviewed / Open Access
• [Journal Article] Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases (2020)
  • Author(s): Suzumura A, Terao R, Kaneko H
  • Journal Title: Antioxidants (Basel) Volume: 26 Issue: 10 Pages: 920-920
  • DOI: 10.3390/antiox9100920
  • Peer Reviewed / Open Access
• [Journal Article] Biological Characteristics of Subsilicone Oil Fluid and Differences With Other Ocular Humors. (2019)
  • Author(s): Shimizu H, Kaneko H, Suzumura A, Takayama K, Namba R, Funahashi Y, Kataoka K, Iwase T, Hwang SJ, Ito S, Yamada K, Ueno S, Ito Y, Terasaki H.
  • Journal Title: Transl Vis Sci Technol Volume: 8 Issue: 1 Pages: 28-28
  • DOI: 10.1167/tvst.8.1.28
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Vascular maturity of type 1 and type 2 choroidal neovascularization evaluated by optical coherence tomography angiography (2019)
  • Author(s): Nakano Y, Kataoka K, Takeuchi J, Fujita A, Kaneko H, Shimizu H, Ito Y, Terasaki H
  • Journal Title: PLoS One. Volume: 14 Issue: 4 Pages: e0216304-e0216304
  • DOI: 10.1371/journal.pone.0216304
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In Vitro Epiretinal Membrane Model and Antibody Permeability: Relationship With Anti-VEGF Resistance in Diabetic Macular Edema (2019)
  • Author(s): Namba R, Kaneko H, Suzumura A, Shimizu H, Kataoka K, Takayama K, Yamada K, Funahashi Y, Ito S, Nonobe N, Terasaki H
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 60 Issue: 8 Pages: 2942-2949
  • DOI: 10.1167/iovs.19-26788
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Silicone oil-associated retinal light exposure under a surgical microscope (2018)
  • Author(s): Yamada K, Kaneko H, Tsunekawa T, Shimizu H, Suzumura A, Namba R, Takeuchi J, Kataoka K, Takayama K, Inoue M, Ito Y, Terasaki H.
  • Journal Title: Acta Ophthalmol. Volume: - Issue: 5
  • DOI: 10.1111/aos.14038
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] シリコーンオイルによる網膜フェロトーシス (2021)
  • Author(s): 兼子 裕規
  • Organizer: 第125回日本眼科学会総会
• [Presentation] Possible mechanism of silicone-oil related vision loss in intractable retinal diseases (2019)
  • Author(s): Hiroki Kaneko
  • Organizer: ARVO Annual Meeting 2019
  • Int'l Joint Research
• [Presentation] シリコーンオイルの生理 シンポジウム１6「手術から学ぶ網膜生理」 (2019)
  • Author(s): 兼子 裕規
  • Organizer: 第73回臨床眼科学会