JP2008201692A - Method for regenerating visual function - Google Patents

Method for regenerating visual function Download PDF

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JP2008201692A
JP2008201692A JP2007037519A JP2007037519A JP2008201692A JP 2008201692 A JP2008201692 A JP 2008201692A JP 2007037519 A JP2007037519 A JP 2007037519A JP 2007037519 A JP2007037519 A JP 2007037519A JP 2008201692 A JP2008201692 A JP 2008201692A
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gene
viral vector
retina
visual
function
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Hiroshi Tomita
浩史 冨田
Makoto Tamai
信 玉井
Eriko Sugano
江里子 菅野
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Tohoku University NUC
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Abstract

<P>PROBLEM TO BE SOLVED: To provide a viral vector containing a gene of channel option 2, a transgenic animal, and a method for treating nerve by imparting a gene function. <P>SOLUTION: The method for regenerating visual functions by carrying out gene introduction into the eye by using the viral vector is provided. In detail, the viral vector containing the gene of the channel option 2 is provided. The treatment of visual function disorder accompanied with various kinds of eye diseases caused by mutation or the like in the retina of a blind is effectively carried out by the gene introduction to the retina as a model of the regeneration of the visual functions for treating the function disorder of the retina by imparting photoreception ability to the remaining nerve cells. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

本発明は、チャンネルオプション２の遺伝子を含むウイルスベクターとトランスジェニック動物、ならびに遺伝子機能を賦与することによる神経治療方法に関する。   The present invention relates to a viral vector containing a gene of channel option 2, a transgenic animal, and a neurotherapeutic method by imparting gene function.

詳細には、本発明はウイルスベクターを用いて眼内に遺伝子導入を行うことで視覚機能を再生する方法を提供する。詳細には、本発明は、チャンネルオプション２の遺伝子を含むウイルスベクターを提供し、残存する神経細胞に光受容能を賦与し、網膜の機能障害を治療する視覚機能再生のモデルとして、網膜へ遺伝子導入することで、失明者の網膜や変異等に起因する各種の眼疾患に伴う視覚機能障害の治療に有効である。   Specifically, the present invention provides a method for regenerating visual function by introducing a gene into the eye using a viral vector. Specifically, the present invention provides a viral vector containing the gene of channel option 2, and provides a gene to the retina as a model of visual function regeneration that imparts photoreceptive capacity to remaining neurons and treats retinal dysfunction. Introducing it is effective in treating visual dysfunction associated with various eye diseases caused by the retina and mutation of the blind.

本発明は、チャンネルオプション２の遺伝子を含むウイルスベクターとトランスジェニック動物及び遺伝子機能を用いた神経治療方法に関する。   The present invention relates to a viral vector containing a gene of channel option 2, a transgenic animal, and a neurotherapeutic method using gene function.

実験動物モデルは、遺伝子の役割を理解するための重要な手段である。特定遺伝子を有する動物を用いての検証には、遺伝子機能の研究にとって計り知れないほど貴重であり、そしてヒトにおける同様な発現を有する疾患の原因となる遺伝子および／または機構の予期せぬ発見につながっている。これらの遺伝的に操作された動物はまた、種々の疾患および障害のための治療的処置を同定および試験するためにも非常に有用である。   Experimental animal models are an important tool for understanding the role of genes. Validation with animals with specific genes is invaluable for the study of gene function, and for the unexpected discovery of genes and / or mechanisms responsible for diseases with similar expression in humans linked. These genetically engineered animals are also very useful for identifying and testing therapeutic treatments for various diseases and disorders.

失明は、習慣病及び遺伝による神経障害、環境因子に関与していると推察される。一旦失われた視機能を再生する方法は皆無であり、唯一の方法として、世界的に工学的技術を利用した人工網膜が研究されている。   It is surmised that blindness is involved in habitual diseases, genetic neuropathy, and environmental factors. There is no way to regenerate the visual function once lost, and as the only method, artificial retina using engineering technology is studied worldwide.

本発明の請求項１に記載の視覚機能の再生方法は、
ウイルスベクターを用いて眼内に遺伝子導入を行うことで視覚機能を再生する方法であって、あらかじめアデノ随伴ウイルスのウイルスベクターを生成する方法と、チャンネルオプション２を含むウイルスベクターを用いて網膜細胞にチャンネルオプション２のＤＮＡを導入し、光受容細胞とすることを具備することを特徴としている。 According to the first aspect of the present invention, there is provided a visual function reproducing method.
A method for regenerating visual functions by introducing a gene into an eye using a viral vector, a method of generating a viral vector of an adeno-associated virus in advance, and a viral vector containing channel option 2 to a retinal cell. It is characterized by introducing a DNA of channel option 2 into a photoreceptor cell.

チャネルオプシン２遺伝子導入による遺伝盲ラットの視機能再建の実験を行った。   Experiments were carried out on the reconstruction of visual function in genetically blind rats by introducing channel opsin 2 gene.

網膜の光伝達様式は、一次ニューロンである視細胞で光を受容し、二次ニューロンである双極細胞、水平細胞で情報処理が行われた後、三次ニューロンの神経節細胞を介して脳に情報が伝達される。加齢黄斑変性や網膜色素変性などの疾患では一次ニューロンである視細胞が選択的に障害されるため、その他のニューロンが生存していたとしても、光を受容することができなくなり、失明に至る。これらの疾患に対する治療法はなく、現在、唯一の視機能再建方法として、工学的技術を用いた人工網膜が世界中で研究されている。しかし、現在試作されている人工網膜チップの網膜刺激電極の数は１００個程度であり、約１００万個存在する網膜神経節細胞の機能を代用することは不可能である。   The light transmission mode of the retina receives light in the photoreceptor cells, which are primary neurons, processes information in the secondary cells, bipolar cells, and horizontal cells, and then transmits information to the brain via the ganglion cells of the tertiary neurons. Is transmitted. In diseases such as age-related macular degeneration and retinitis pigmentosa, the primary neurons are selectively damaged, so even if other neurons are alive, they cannot accept light and lead to blindness . There is no cure for these diseases, and currently, the only reconstructing method of visual function is researching artificial retina using engineering techniques all over the world. However, the number of retinal stimulating electrodes of an artificial retinal chip that is currently being prototyped is about 100, and the function of retinal ganglion cells, which are about 1 million, cannot be substituted.

緑藻類より単離された光受容能とイオンチャネル能を有するチャネルオプシン2は、その特性から細胞に導入することで細胞に光受容能を賦与することができることが知られている。我々はウイルスベクターを用いて、チャネルオプシン２遺伝子を遺伝盲ラットの残存する網膜神経細胞に導入することで視機能を再建できるかどうかについて、電気生理学的および行動学的に調べた。   It is known that channel opsin 2 having photoreceptive ability and ion channel ability isolated from green algae can impart photoreceptive ability to cells by introducing it into the cell. We examined whether the visual function can be reconstructed by introducing the channel opsin 2 gene into the remaining retinal neurons of a genetically blind rat using a viral vector.

チャネルオプシン2遺伝子をアデノ随伴ウイルスベクターを用いて、遺伝盲ラットの網膜細胞に導入した結果、導入前に全く認められなかった視覚誘発電位が記録された。この結果はチャネルオプシン２遺伝子導入によって、何らかの視覚情報が脳に伝達されていることを示している。どのような視覚が得られているかを調べるために、ラットの首振り運動により調べた。この結果、遺伝子導入されたラットは青白の縞模様を判別できることが明らかとなった。また、遺伝子導入効率を調べた結果、網膜神経節細胞の約３０％に導入され、３０万個の細胞が光受容細胞になったと考えられる。   As a result of introducing channel opsin 2 gene into retinal cells of genetically blind rats using an adeno-associated virus vector, visual evoked potentials that were not observed at all before the introduction were recorded. This result shows that some visual information is transmitted to the brain by channel opsin 2 gene introduction. In order to investigate what kind of vision was obtained, it was examined by swinging the rat. As a result, it was revealed that the transgenic rat can discriminate blue-white stripes. Moreover, as a result of examining the gene transfer efficiency, it was considered that about 30% of retinal ganglion cells were introduced and 300,000 cells became photoreceptor cells.

以上のように、チャネルオプシン２遺伝子の導入によって、視機能を再建できることが明らかとなった。   As described above, it was revealed that visual function can be reconstructed by introducing the channel opsin 2 gene.

Claims (1)

ウイルスベクターを用いて眼内に遺伝子導入を行うことで視覚機能を再生する方法であって、あらかじめアデノ随伴ウイルスのウイルスベクターを生成する方法と、チャンネルオプション２を含むウイルスベクターを用いて網膜細胞にチャンネルオプション２のＤＮＡを導入し、光受容細胞とすることを具備することを特徴とする視覚機能の再生方法。   A method for regenerating visual functions by introducing a gene into an eye using a viral vector, a method for generating a viral vector of an adeno-associated virus in advance, and a retinal cell using a viral vector containing channel option 2 A method for regenerating visual function, comprising introducing DNA of channel option 2 into a photoreceptor cell.
JP2007037519A 2007-02-19 2007-02-19 Method for regenerating visual function Pending JP2008201692A (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009536219A (en) * 2006-05-04 2009-10-08 ウェイン・ステート・ユニバーシティー Recovery of visual response by in vivo delivery of rhodopsin diffusion

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009536219A (en) * 2006-05-04 2009-10-08 ウェイン・ステート・ユニバーシティー Recovery of visual response by in vivo delivery of rhodopsin diffusion

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