網膜細胞の「若返り」で緑内障マウスの視力回復、ｉＰＳ作製過程を利用　米研究

【東京ＡＦＰ＝時事】老化した細胞を「若返らせる」技術を用いてマウスの視力を回復することに成功したとの研究結果が2日、英科学誌「ネイチャー」（電子版）に掲載された。細胞レベルで時間を事実上巻き戻し、けがや病気、加齢によって損傷を負った細胞の治癒能力を高めるという、画期的で興味をそそられる治療法の可能性を示している。（写真は資料写真）
　論文の上席著者を務めたハーバード医科大学院のデービッド・シンクレア教授（遺伝学）は「特に、認知症などの効果的な治療法のない分野で、加齢や病気によって機能しなくなった臓器・組織を若返らせることができる」と喜びを表明。「緑内障の治療で２年以内に臨床試験を行いたい」とＡＦＰに語った。
　研究チームは、人工多能性幹細胞（ｉＰＳ細胞）の作製過程を利用。四つのたんぱく質を発現させて細胞の分化を白紙状態に戻すのではなく、ＯＳＫと呼ばれる三つのたんぱく質を発現させることで細胞を若々しい状態まで回復させるカクテルを作製した。
　研究では、軸索と呼ばれる部位で脳とつながっている網膜神経節細胞に着目した。軸索は視神経を形成し、けがや加齢、病気で損傷すると視力低下や失明を引き起こす。
　まず、視神経を損傷したマウスの目にＯＳＫを注入すると、網膜神経節細胞の生存数は２倍に、神経再生レベルは５倍に増加した。
　次に、人間の失明原因第１位である緑内障への影響を調べるため、眼圧を上昇させて視神経障害を再現したマウス数十匹にＯＳＫ治療を施したところ、「著しい」効果がみられた。
　研究は１年にわたって行われたが、マウスに副作用は見られなかった。【翻訳編集ＡＦＰＢＢＮｅｗｓ】
〔ＡＦＰ＝時事〕（2020/12/04-11:14）

Scientists said Wednesday they have restored sight in mice using a milestone treatment that returns cells to a more youthful state and could one day help treat glaucoma and other age-related diseases.
The process offers the tantalising possibility of effectively turning back time at the cellular level, helping cells recover the ability to heal damage caused by injury, disease and age.
I'm excited about being able to rejuvenate organs and tissues that fail due to ageing and disease, especially where there are no effective treatments, such as dementia, senior author of the study David Sinclair told AFP.
We hope to treat glaucoma in human patients (at the trial stage) in two years, added Sinclair, a professor of genetics at Harvard Medical School.
The treatment is based on the properties that cells have when the body is developing as an embryo. At that time, cells can repair and regenerate themselves, but that capacity declines rapidly with age.
The scientists reasoned that if cells could be induced to return to that youthful state, they would be able to repair damage.
To turn back the clock, they modified a process usually used to create the blank slate cells known as induced pluripotent stem cells.
Those cells are created by injecting a cocktail of four proteins that help reprogramme a cell.
The team did not want to reprogramme cells all the way back to that blank-slate status, but to restore them to a more youthful condition.
So they tweaked the cocktail, using just three of the youth-restoring proteins -- dubbed OSK -- in the hope they could turn the clock back to just the right point.
They targeted the retinal ganglion cells in the eye, which are linked to the brain through connections called axons.
These axons form the optic nerve -- and damage to them caused by injury, ageing or disease causes poor vision and blindness.
To test the effects of the cocktail, they first injected OSK into the eyes of mice with optic nerve injuries.
They saw a twofold increase in the number of surviving retinal ganglion cells and a fivefold increase in nerve regrowth.
The treatment allowed the nerves to grow back towards the brain. Normally they would simply die, Sinclair said.
- 'Great excitement' -
With signs OSK could reverse damage caused by injury, the team turned to countering the effects of disease -- specifically glaucoma, which is the leading cause of blindness in humans.
They replicated the conditions of the disease, where a build-up of pressure in the eye damages the optic nerve, in several dozen mice.
Those who received the OSK treatment saw significant benefits, according to the study published in the journal Nature.
Tests showed that half of the visual acuity lost from increased intraocular pressure was restored.
The treatment offered similarly promising results in elderly mice with poor vision caused by age.
After the cocktail was injected, the mice's vision improved and their optic nerve cells displayed electrical signals and other features akin to those in younger mice.
The study was conducted over the course of a year, and the mice displayed no side effects.
Andrew Huberman, a neuroscientist at Stanford University School of Medicine, who was not involved in the research, said the findings were bound to ignite great excitement.
The results will need to be confirmed in further animal tests, with a potentially long path before humans can be treated, but Huberman said they nevertheless represented a milestone in the field.
The effects of OSK in people remain to be tested but the existing results suggest that OSK is likely to reprogramme brain neurons across species, he wrote in a review commissioned by Nature.
For decades, it was argued that understanding normal neural developmental processes would one day lead to the tools to repair the aged or damaged brain... (this) work makes it clear: that era has now arrived.