HSF-1 is indispensable for injured optic nerve regeneration.

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K05725
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
• Research Institution: Kanazawa University
• Principal Investigator: Sugitani Kayo 金沢大学, 保健学系, 准教授 (20162258)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: zebrafish / optic nerve regeneration / retina / transglutaminase 2 / heat shock factor 1 / Yamanaka factors / reprgramming / antiapoptosis

Outline of Final Research Achievements

Unlike in mammals, fish central nervous system neurons can regrow axons and restore their function after nerve injury. In this study, we used a zebrafish optic nerve injury model to analyze molecules induced during the acute phase (<24 hours) of the regenerative process. The results revealed that the three Yamanaka factors, klf 4, oct 4, and sox 2, are activated in the damaged retina within a few hours. This activation required increased expression of HSF1 in the retina. Early expression of HSF1 was also important for avoiding apoptosis. Further, activation of HSF1 required immediate upregulation of Transglutaminase 2 in the damaged retina. Expression of these molecules may avoid neuronal damage after optic nerve injury, and expression of Yamanaka factors may contribute to induction of reprogramming to form new optic nerve.

Free Research Field

神経生理学，神経科学

Academic Significance and Societal Importance of the Research Achievements

魚類の網膜-視神経-視蓋からなる視覚系は，中枢神経軸索再生のモデルとしてよく研究されており基礎的データの蓄積が大きい。本研究により神経軸索の再生あるいは創傷治癒のスイッチを握るかもしれない分子の活性化機構が明らかとなれば，中枢神経組織の損傷直後に発現誘導される急性相反応物質の生理学的意義の解明に繋がると考えられる。また，この実験系では山中ファクターの誘導が視神経クラッシュによって自然な治癒過程として網膜で起こるため、本研究が進展すれば，ヒトの脊髄損傷など中枢神経軸索損傷に対し治療効果のある分子が発見されるきっかけを掴める可能性がある。