Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors

被引：86

作者：

Ribeiro, Joana ^{[1
,3
]}

Procyk, Christopher A. ^{[1
,4
]}

West, Emma L. ^{[1
,4
]}

O'Hara-Wright, Michelle ^{[1
]}

Martins, Monica F. ^{[1
]}

Khorasani, Majid Moshtagh ^{[1
,4
]}

Hare, Aura ^{[1
,4
]}

Basche, Mark ^{[1
,4
]}

Fernando, Milan ^{[1
]}

Goh, Debbie ^{[1
]}

Jumbo, Neeraj ^{[1
]}

Rizzi, Matteo ^{[1
,4
]}

Powell, Kate ^{[1
,4
]}

Tariq, Menahil ^{[1
]}

Michaelides, Michel ^{[1
]}

Bainbridge, James W. B. ^{[1
]}

Smith, Alexander J. ^{[1
,4
]}

Pearson, Rachael A. ^{[1
,4
]}

Gonzalez-Cordero, Anai ^{[1
,5
]}

Ali, Robin R. ^{[1
,2
,4
]}

机构：

[1] UCL Inst Ophthalmol, 11-43 Bath St, London EC1V 9EL, England

[2] Univ Michigan, Kellogg Eye Ctr, 1000 Wall St, Ann Arbor, MI 48105 USA

[3] Stanford Univ, Lorry I Lokey Stem Cell Res Bldg,265 Campus Dr, Palo Alto, CA USA

[4] Kings Coll London, Guys Hosp, Ctr Cell & Gene Therapy, Tower Wing, London SE1 9RT, England

[5] Univ Sydney, Childrens Med Res Inst, 214 Hawkesbury Rd, Westmead, NSW 2145, Australia

来源：

CELL REPORTS | 2021年 / 35卷 / 03期

基金：

英国医学研究理事会; 欧洲研究理事会;

关键词：

STAGE RETINAL-DEGENERATION; GANGLION-CELL; BIPOLAR CELLS; MOUSE MODEL; ACHROMATOPSIA; SHEETS; MICE; INTEGRATION; MECHANISM; RESTORES;

D O I：

10.1016/j.celrep.2021.109022

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Age-related macular degeneration and other macular diseases result in the loss of light-sensing cone photo-receptors, causing irreversible sight impairment. Photoreceptor replacement may restore vision by transplanting healthy cells, which must form new synaptic connections with the recipient retina. Despite recent advances, convincing evidence of functional connectivity arising from transplanted human cone photoreceptors in advanced retinal degeneration is lacking. Here, we show restoration of visual function after transplantation of purified human pluripotent stem cell-derived cones into a mouse model of advanced degeneration. Transplanted human cones elaborate nascent outer segments and make putative synapses with recipient murine bipolar cells (BCs), which themselves undergo significant remodeling. Electrophysiological and behavioral assessments demonstrate restoration of surprisingly complex light-evoked retinal ganglion cell responses and improved light-evoked behaviors in treated animals. Stringent controls exclude alternative explanations, including material transfer and neuroprotection. These data provide crucial validation for photoreceptor replacement therapy and for the potential to rescue cone-mediated vision.

引用

页数：24

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