JP2019000060A - 白内障の誘導方法、白内障のモデル生物、白内障の予防剤ならびに治療剤のスクリーニング方法、および、白内障誘導剤 - Google Patents
白内障の誘導方法、白内障のモデル生物、白内障の予防剤ならびに治療剤のスクリーニング方法、および、白内障誘導剤 Download PDFInfo
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Images
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Abstract
Description
(i)上記採取された水晶体、または、非ヒト生物の水晶体に対して、紫外線、または、放射線を照射すること、
(ii)上記採取された水晶体、または、非ヒト生物の水晶体に対して、DNAの損傷を引き起こす物質を接触させること。
[1−1.白内障]
本明細書において「白内障」とは、水晶体に混濁(例えば、白濁)を生じる疾患を意図する。白内障によって水晶体に生じる混濁には、例えば、皮質混濁;核混濁;後嚢下混濁;皮質スポーク状混濁;前嚢下混濁;線維ひだ、水隙、または、核周囲の徹照下点状混濁;水疱;点状混濁;冠上混濁などの類型がある。「白内障」の種類としては、加齢白内障、および、併発白内障(例えば、糖尿病白内障、先天白内障、外傷性白内障、アトピー白内障、放射線白内障、および、ステロイド白内障)などを挙げることができる。
本明細書において「予防剤」とは、予防効果をもたらす薬剤を意図する。当該予防効果とは、以下に例示される効果を意図するが、これらに限定されるものではない。
(1)予防剤を投与しなかった場合と比較して、予防剤を投与した場合には、疾患に係る1つ以上の症状の発症を防止する、または、発症のリスクを低減する。
(2)予防剤を投与しなかった場合と比較して、予防剤を投与した場合には、疾患に係る1つ以上の症状の再発を防止する、または、再発のリスクを低減する。
(3)予防剤を投与しなかった場合と比較して、予防剤を投与した場合には、疾患に係る1つ以上の症状の兆候が生じることを防止する、または、兆候が生じるリスクを低減する。
本明細書において「治療剤」とは、治療効果をもたらす薬剤を意図する。当該治療効果とは、以下に例示される効果を意図するが、これらに限定されるものではない。
(1)治療剤を投与しなかった場合と比較して、治療剤を投与した場合には、疾患に係る1つ以上の症状の重症度を低減する。
(2)治療剤を投与しなかった場合と比較して、治療剤を投与した場合には、疾患に係る1つ以上の症状の重症度の増加、または、重症度の進行を防止する。
(3)治療剤を投与しなかった場合と比較して、治療剤を投与した場合には、疾患に係る1つ以上の症状の重症度の増加速度、または、重症度の進行速度を低減する。
本実施の形態の白内障誘導剤は、DNA(例えば、染色体DNAなど)の損傷を引き起こす物質を有効成分として含有している。
本実施の形態の白内障の誘導方法は、採取された水晶体のDNA、または、非ヒト生物の水晶体のDNAに損傷を与える損傷工程を有している。
(i)上記採取された水晶体、または、非ヒト生物の水晶体に対して、紫外線、または、放射線(例えば、α線、β線、γ線、または、X線)を照射すること、または、
(ii)上記採取された水晶体、または、非ヒト生物の水晶体に対して、DNAの損傷を引き起こす物質を接触させること。
本実施の形態の白内障のモデル生物は、上述した〔2.白内障の誘導方法〕に記載の方法によって得られるモデル生物である。例えば、当該モデル生物を用いれば、後述する〔4.白内障の予防剤または治療剤のスクリーニング方法〕を行うことができる。また、当該モデル生物を用いれば、白内障の発症メカニズムを解明することができる。
本実施の形態の白内障の予防剤のスクリーニング方法は、採取された水晶体、または、非ヒト生物の水晶体と、被検物質と、を接触させる接触工程と、当該接触工程の後で、上記採取された水晶体のDNA、または、上記非ヒト生物の水晶体のDNAに損傷を与える損傷工程と、を有している。
6週齢のSDラット(三協ラボサービス社製)の左右の眼球から、水晶体を摘出した。右眼から摘出した水晶体は、M199培地(SIGMA社製)を用いて培養した。一方、左眼から摘出した水晶体は、(i)M199培地に、4mM、2mM、若しくは、1mMのMMS(methyl methanesulfonate)を添加した培地、または、(ii)M199培地に、800μg/mL、400μg/mL、若しくは、200μg/mLのブレオマイシンを添加した培地、を用いて培養した。
6週齢のSDラット(三協ラボサービス社製)の左右の眼球から、水晶体を摘出した。右眼から摘出した水晶体は、M199培地(SIGMA社製)を用いて培養した。一方、左眼から摘出した水晶体は、M199培地に、400mM、40mM、4mM、1mM、0.5mM、または、0.1mMのMMS(methyl methanesulfonate)を添加した培地、を用いて培養した。
Claims (9)
- 採取された水晶体のDNA、または、非ヒト生物の水晶体のDNAに損傷を与える損傷工程を有する、白内障の誘導方法。
- 上記白内障は、加齢白内障、先天白内障、外傷性白内障、アトピー白内障、放射線白内障、ステロイド白内障、または、糖尿病白内障である、請求項1に記載の白内障の誘導方法。
- 上記損傷工程は、上記採取された水晶体、または、上記非ヒト生物の水晶体に所定の強度の刺激を加えることによって、DNAに損傷を与える工程であり、
上記刺激は、当該刺激を加えた後の当該水晶体の断面の一部分のみが混濁する程度の強度の刺激である、請求項1または2に記載の白内障の誘導方法。 - 上記損傷工程は、以下の(i)および/または(ii)を包含する、請求項1〜3の何れか1項に記載の白内障の誘導方法:
(i)上記採取された水晶体、または、非ヒト生物の水晶体に対して、紫外線、または、放射線を照射すること、
(ii)上記採取された水晶体、または、非ヒト生物の水晶体に対して、DNAの損傷を引き起こす物質を接触させること。 - 請求項1〜4の何れか1項に記載の方法によって得られる、白内障のモデル生物。
- 採取された水晶体、または、非ヒト生物の水晶体と、被検物質と、を接触させる接触工程と、
上記接触工程の後で、上記採取された水晶体のDNA、または、上記非ヒト生物の水晶体のDNAに損傷を与える損傷工程と、を有する、白内障の予防剤のスクリーニング方法。 - 採取された水晶体のDNA、または、非ヒト生物の水晶体のDNAに損傷を与える損傷工程と、
上記損傷工程の後で、上記採取された水晶体、または、上記非ヒト生物の水晶体と、被検物質と、を接触させる接触工程と、を有する、白内障の治療剤のスクリーニング方法。 - DNAの損傷を引き起こす物質を有効成分として含有している、白内障誘導剤。
- 上記DNAの損傷を引き起こす物質は、DNAのアルキル化、DNAの切断、DNAへの化合物の付加、または、DNAへの塩基類似体の挿入を引き起こすものである、請求項8に記載の白内障誘導剤。
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