Photoreceptors derived from human stem cells then transplanted to blind mice allowed the rodents to perceive light up to a year after the injection, according to scientists at Novato-based Buck Institute for Research on Aging.
Findings by Buck faculty member Deepak Lamba were published Jan. 12 in the Cell Stem Cell scientific journal, part of Cell Press based in Cambridge, Mass.
“This turned into a nice story of long-term restoration of vision in completely blind mice,” Lamba said. “These mice can now perceive light.”
Lamba’s pioneering research explores treatment for degenerative vision disorders including macular degeneration and retinitis pigmentosa using embryonic stem cells to generate human retinal cells. He derives patient-specific stem cells by reprogramming skin cells into pluripotent stem cells then converting them to retinal cells.
When stem cells are implanted into a mouse or human, the cells are attacked by the body’s immune system and rejected. Lamba studied how immune-system rejection ruined attempts to use stem cells to regenerate sight in humans and looked for ways to suppress the immune response.
The retina in the back of the eyeball has photoreceptive cells that respond to light then trigger nerve impulses carried by the optic nerve to the brain, which forms a visual image based on information delivered.
To study immune-system rejection of stem cells transplanted into the eye, Lamba used a mouse strain that lacks a specific immune-cell receptor and cannot reject transplanted foreign cells. The critters are called “immunodeficient IL2-receptor-gamma-null mice” and lack the IL2ry receptor that humans have in a healthy immune system.
“They are otherwise healthy and normal, including in their vision,” said Jie Zhu, a postdoctoral researcher who came to Lamba’s laboratory three years ago. Without immune rejection, 10 times as many retinal cells survived after being derived from human embryonic stem cells.
Lamba’s team transplanted the stem-cell-derived photoreceptors into another type of mouse called CRX-null, which is congenitally blind. Some of these mice could perceive light up to a year after transplantation.
Lamba isn’t the only scientist chasing the use of stem cells to restore vision. A study published Jan. 10 in Stem Cell Reports showed that retinal tissue derived from mouse-induced pluripotent stem cells connected with nearby cells and responded to light stimulus after transplantation to mice that were blind due to end-stage retinal degeneration. Half the blind mice had their visual function restored enough to avoid electric shocks by responding to a light warning signal.
The study was conducted by Masayo Takahashi at the RIKEN Center for Developmental Biology in Kobe, Japan.
“One cannot expect to restore practical vision at the moment,” she said in a story published in Maryland-based Science Daily. “We hope to restore more substantial vision in the future.”
Lamba, who practiced as a physician in Mumbai, India, earned a master’s degree in bioengineering from University of Illinois, where he worked on a chemically stimulating retinal prosthesis. He did doctoral work at University of Washington in Seattle, where he generated and transplanted retinal cells derived from human embryonic stem cells and induced pluripotent stem cells.
As the North Bay Business Journal reported in May 2016, Buck Institute scientist Xianmin Zeng co-founded a Novato-based company called XCell Sciences that sells 20 engineered lines of induced pluripotent stem cells, neural cells and models to promote gene-editing research on diseases including Parkinson’s, Alzheimer’s, amyotrophic lateral sclerosis, Huntington’s Disease, schizophrenia and autism.