Mechanisms of retrotransposon accumulation in age-related macular degeneration

• Project/Area Number: 18K19961
• Research Category: Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research)
• Allocation Type: Multi-year Fund
• Review Section: Biological Sciences
• Research Institution: University of Tsukuba
• Principal Investigator: Fukuda Shinichi 筑波大学, 医学医療系, 准教授 (80643246)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥61,620,000 (Direct Cost: ¥47,400,000、Indirect Cost: ¥14,220,000)
• Keywords: 逆転写 / Alu / 加齢黄斑変性 / cDNA / レトロトランスポゾン / DNA蓄積 / 黄斑変性 / 黄斑変性症 / TREX1遺伝子欠損

Outline of Final Research Achievements

Dry type age-related macular degeneration is a disease that causes serious vision loss with age. We started an independent laboratory, the Laboratory of Advanced Vision Science , at the University of Tsukuba, and has demonstrated that Alu RNA accumulates in the retinal pigment epithelium of patients with dry type age-related macular degeneration through a mechanism very similar to aging. And Alu cDNA is generated by reverse transcription, inducing retinal pigment epithelial cell death. The results were reported in PNAS and Science Advanced as the first author (Fukuda S, PNAS 2021; FukudaS Sci Adv 2021).

Academic Significance and Societal Importance of the Research Achievements

萎縮型加齢黄斑変性は、加齢とともに深刻な視力の低下を引き起こす疾患であり、現在有効な治療法はない。本研究成果は、新しい遺伝情報の流れを見出し、萎縮型加齢黄斑変性のメカニズムの一端を解明、逆転写を阻害する事が萎縮型加齢黄斑変性の悪化の予防に繋がる可能性を示唆した。

Research Products

• [Int'l Joint Research] バージニア大学(米国)
• [Int'l Joint Research] バージニア大学/ケンタッキー大学(米国)
• [Int'l Joint Research] バージニア大学/ケンタッキー大学/Dorn Research Institute(米国)
• [Int'l Joint Research] ローザンヌ大学(スイス)
• [Int'l Joint Research] Paul Ehrlich Institute(ドイツ)
• [Int'l Joint Research] バージニア大学(米国)
• [Journal Article] Subretinal injection in mice to study retinal physiology and disease. (2022)
  • Author(s): Huang P, Narendran S, Pereira F, Fukuda S, Nagasaka Y, Apicella I, Yerramothu P, Marion K, Cai X, Sadda S, Gelfand B, Ambati J.
  • Journal Title: Nature Protocols Volume: in press Issue: 6 Pages: 1468-1485
  • DOI: 10.1038/s41596-022-00689-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Learning Curve of Murine Subretinal Injection Among Clinically Trained Ophthalmic Surgeons (2022)
  • Author(s): Huang P, Narendran S, Pereira F, Fukuda S, Nagasaka Y, Apicella I, Yerramothu P, Marion K, Cai X, Sadda S, Gelfand B, Ambati J.
  • Journal Title: Transl Vis Sci Technol . Volume: 11 Issue: 3 Pages: 13-13
  • DOI: 10.1167/tvst.11.3.13
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Detection of Anterior Hyaloid Membrane Detachment Using Deep-Range Anterior Segment Optical Coherence Tomography (2022)
  • Author(s): Mori Haruhiro、Ueno Yuta、Fukuda Shinichi、Oshika Tetsuro
  • Journal Title: Journal of Clinical Medicine Volume: 11 Issue: 11 Pages: 3057-3057
  • DOI: 10.3390/jcm11113057
  • Peer Reviewed / Open Access
• [Journal Article] Effect of the COVID-19 pandemic on antibiotic consumption: A systematic review comparing 2019 and 2020 data (2022)
  • Author(s): Fukushige Mizuho、Ngo Nhat-Hoang、Lukmanto Donny、Fukuda Shinichi、Ohneda Osamu
  • Journal Title: Frontiers in Public Health Volume: 10 Pages: 946077-946077
  • DOI: 10.3389/fpubh.2022.946077
  • Peer Reviewed / Open Access
• [Journal Article] Label-free metabolic imaging of non-alcoholic-fatty-liver-disease (NAFLD) liver by volumetric dynamic optical coherence tomography. (2022)
  • Author(s): Mukherjee P, Fukuda S, Lukmanto D, Yamashita T, Okada K, Makita S, El-Sadek IA, Arata Miyazawa, Zhu L, Morishita R, Lichtenegger A, Oshika T, Yasuno Y.
  • Journal Title: Biomed Opt Express. Volume: 13 Issue: 7 Pages: 4071-4086
  • DOI: 10.1364/boe.461433
  • Peer Reviewed / Open Access
• [Journal Article] Label-free functional and structural imaging of liver microvascular complex in mice by Jones matrix optical coherence tomography (2021)
  • Author(s): Mukherjee Pradipta、Miyazawa Arata、Fukuda Shinichi、Yamashita Toshiharu、Lukmanto Donny、Okada Kosuke、El-Sadek Ibrahim Abd、Zhu Lida、Makita Shuichi、Oshika Tetsuro、Yasuno Yoshiaki
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 20054-20054
  • DOI: 10.1038/s41598-021-98909-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Alu complementary DNA is enriched in atrophic macular degeneration and triggers retinal pigmented epithelium toxicity via cytosolic innate immunity (2021)
  • Author(s): Fukuda Shinichi、Terasaki Hiroko、Oshika Tetsuro、Bhattarai Deepak、Kim Kyung Bo、Feldman Sanford H.、Aguirre J. Ignacio、Hinton David R.、Kerur Nagaraj、Sadda Srinivas R.、Schumann Gerald G.、Gelfand Bradley D.、Ambati Jayakrishna
  • Journal Title: Science Advances Volume: 7 Issue: 40
  • DOI: 10.1126/sciadv.abj3658
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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 (2021)
  • Author(s): Kaneko H, Hirata N, Shimizu H, Kataoka K, Nonobe N, Mokuno K, Terasaki H.
  • Journal Title: Jpn J Ophthalmol Volume: 65 Issue: 6 Pages: 380-387
  • DOI: 10.1073/pnas.2022751118
  • NAID: 40022562044
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nucleoside reverse transcriptase inhibitors and Kamuvudines inhibit amyloid-β induced retinal pigmented epithelium degeneration (2021)
  • Author(s): Narendran S, Pereira F, Yerramothu P, Apicella I, Wang S, Ambati K, Hirahara S, Kim Y, Ambati M, Ambati V, Huang P, Varshney A, Nagasaka Y, Fukuda S, Baker K, Marion K, Deussing J, Sadda S, Gelfand B, and Ambati J.
  • Journal Title: Signal Transduct Target Ther Volume: 6 Issue: 1 Pages: 149-149
  • DOI: 10.1038/s41392-021-00537-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Optical coherence tomography-based tissue dynamics imaging for longitudinal and drug response evaluation of tumor spheroids (2020)
  • Author(s): Abd El-Sadek Ibrahim、Miyazawa Arata、Tzu-Wei Shen Larina、Makita Shuichi、Fukuda Shinichi、Yamashita Toshiharu、Oka Yuki、Mukherjee Pradipta、Matsusaka Satoshi、Oshika Tetsuro、Kano Hideaki、Yasuno Yoshiaki
  • Journal Title: Biomedical Optics Express Volume: 11 Issue: 11 Pages: 6231-6231
  • DOI: 10.1364/boe.404336
  • NAID: 120007192296
  • Peer Reviewed / Open Access
• [Journal Article] Repurposing anti-inflammasome NRTIs for improving insulin sensitivity and reducing type 2 diabetes development. (2020)
  • Author(s): Ambati J, Magagnoli J, Leung H, Wang S, Andrews C, Fu D, Pandey A, Sahu S, Narendran S, Hirahara S, Fukuda S, Sun J, Pandya L, Ambati M, Pereira F, Varshney A, Cumimngs T, Hardin J, Edun B, Bennett C, Ambati K, Fowler B, Kerur N, Rover C, Leitinger N, Werner B, Sutton S, Gelfand B.
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 4737-4737
  • DOI: 10.1038/s41467-020-18528-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Quantification of ex vivo tissue activity by short and long time-course analysis of multifunctional OCT signals (2020)
  • Author(s): Abd El-Sadek Ibrahim、Miyazawa Arata、Shen Larina、Fukuda Shinichi、Yamashita Toshiharu、Oka Yuki、Mukherjee Pradipta、Makita Shuichi、Matsusaka Satoshi、Oshika Tetsuro、Kano Hideaki、Yasuno Yoshiaki
  • Journal Title: Proc. SPIE Volume: 11228 Pages: 83-83
  • DOI: 10.1117/12.2548541
  • Peer Reviewed
• [Journal Article] Chronic Dicerl Deficiency Promotes Atrophic and Neovascular Outer Retinal Pathologies in Mice (2020)
  • Author(s): Wright CB, Uehara H, Kim Y, Yasuma T, Yasuma R, Hirahara S, Makin RD, Apicella I, Pereira F, Nagasaka Y, Narendran S, Fukuda S, Albuquerque R, Fowler BJ, Bastos-Carvalho A, Georgel P, Hatada I, Chang B, Kerur N, Ambati BK, Ambati J, Gelfand BD.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 117 Issue: 5 Pages: 2579-2587
  • DOI: 10.1073/pnas.1909761117
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Comparison of anterior segment and lens biometric measurements in patients with cataract (2020)
  • Author(s): Fukuda S, Ueno Y, Fujita A, Mori H, Tasaki K, Murakami T, Beheregaray S, Oshika T
  • Journal Title: Graefes Arch Clin Exp Ophthalmol Volume: 258 Issue: 1 Pages: 137-146
  • DOI: 10.1007/s00417-019-04482-0
  • Peer Reviewed
• [Journal Article] Quantification of ex-vivo tissue activity by polarization dynamics imaging using Jones matrix optical coherence tomography (2020)
  • Author(s): Mukherjee P, Miyazawa A, Shen L, Fukuda S, Yamashita T, Oka Y, E1-Sadek IA, Makita S, Matsusaka S, Oshika T, Kano H, Yasuno Y
  • Journal Title: Proc. SPIE. Pages: 23-23
  • DOI: 10.1117/12.2573237
  • Peer Reviewed
• [Presentation] Intracellular deposition of retrotransposon in age related macular degeneration. (2022)
  • Author(s): Shinichi Fukuda
  • Organizer: The 12th BRI international Symposium
  • Int'l Joint Research / Invited
• [Presentation] 高深達前眼部OCTによる前部硝子体剥離の観察 (2020)
  • Author(s): 福田慎一、森悠大、上野勇太、藤田亜佳里、長谷川優美、平岡 孝浩、大鹿哲郎
  • Organizer: 第124回日本眼科学会総会
• [Presentation] 日本の医学生は海外の医学生と比較して自らをどのように捉えているかについての検討 (2020)
  • Author(s): 福田慎一、木村友和
  • Organizer: 第52回日本医学教育学会大会
• [Book] Atlas of Anterior Segment Optical Coherence Tomography (2020)
  • Author(s): Fukuda S, Yasuno Y, Oshika T.
  • Total Pages: 249
  • Publisher: Springer Nature Switzerland AG