Retina transplantation improved by manipulating recipient retinal microenvironment

July 11, 2012

A research team in the United Kingdom has found that insulin-like growth factor (IGF1) impacts cell transplantation of photoreceptor precursors by manipulating the retinal recipient microenvironment, enabling better migration and integration of the cells into the adult mouse retina.

Their study is published in the current issue of Cell Transplantation (21:5), now freely available on-line.

"Photoreceptor death is an irreversible process and represents one of the largest causes of untreatable blindness in the developed world," said Dr. Rachael A. Pearson, study co-author and a member of the Department of Genetics, University College London Institute of Ophthalmology. "Stem cell replacement therapy offers a novel strategy for retinal repair, but since it is likely that a large number of cells would be needed to restore vision, enhancement of the process is needed."

In this study, the researchers used adeno-associated viral vectors (AAVs) to introduce three previously reported to play a role in photoreceptor development - IGF1, fibroblast growth factor (FGF2) and ciliary neurotrophic factor (CNTF) - into the retinas of . At three weeks post-transplantation, the number of integrated, differentiated present in the growth factor-treated retinas was compared to the untreated controls.

The researchers noted that all three growth factors are present during retinal development and all have been shown to affect photoreceptor differentiation. FGF2 has been shown to have varying effects based on the development stage of the cells to which it is applied. In addition, recent studies have shown that CNTF "acts transiently to suppress photoreceptor ."

"AAV mediated expression of IGF1 led to significantly increased levels of cell integration," wrote the researchers. "However, over expression of FGF2 had no significant effect on cell numbers and CNTF led to a significant decrease in cell integration."

They concluded that it was possible to manipulate the environment of the recipient retina for photoreceptor cell transplantation using , and that IGF1 provided a greater response.

"A potential consequence of IGF1 upregulation might be the improved or strengthened synaptic connectivity of the transplanted cells," said Dr. Pearson. "Newly born neurons, including photoreceptors, are vulnerable to pruning and apoptosis if appropriate synaptic connections with downstream targets are not formed and maintained."

The researchers noted that IGF1 has also been associated with the upregulation of brain-derived (BDNF), an important modulator of synaptic plasticity in the adult brain after injury and along with exercise-induced cognitive function.

"This important study demonstrates that, by modifying the environment, growth factors impact cell transplantation survival," said Dr. John Sladek, professor of neurology and pediatrics at the University of Colorado School of Medicine. "While this study focused on the retina, growth factors also are believed to alter and survival in other brain regions which means that these findings should lead to more research on other serious neurological disorders."

Explore further: Photoreceptor transplant restores vision in mice

More information: West, E. L.; Pearson, R. A.; Duran, Y.; Gonzalez-Cordero, A.; Maclaren, R. E.; Smith, A. J.; Sowden, J. C.; Ali, R. R. Manipulation of the recipient retinal environment by ectopic expression of neurotrophic growth factors can improve transplanted photoreceptor integration and survival. Cell Transplant. 21(5):871-887; 2012. http://www.ingentaconnect.com/content/cog/ct/

Related Stories

Photoreceptor transplant restores vision in mice

April 18, 2012
Scientists funded by the Medical Research Council (MRC) have shown for the first time that transplanting light-sensitive photoreceptors into the eyes of visually impaired mice can restore their vision.

Stop signal for leukemia stem cells

August 23, 2011
There are numerous specialized growth factors that are responsible for cells of different tissues of our body to divide and differentiate when needed. These hormone-like factors bind to matching receptors on the surface of ...

Pig stem cell transplants: The key to future research into retina treatment

April 13, 2011
A team of American and Chinese scientists studying the role of stem cells in repairing damaged retina tissue have found that pigs represent an effective proxy species to research treatments for humans. The study, published ...

Recommended for you

Researchers identify potential biomarkers of age-related macular degeneration

September 12, 2017
Patients with any stage of age-related macular degeneration (AMD) carry signs of the disease in their blood that may be found through special laboratory tests, according to a new study led by AMD researchers based at Massachusetts ...

Researchers unlock regenerative potential of cells in the mouse retina

August 28, 2017
Cells within an injured mouse eye can be coaxed into regenerating neurons and those new neurons appear to integrate themselves into the eye's circuitry, new research shows. The findings potentially open the door to new treatments ...

Antioxidant supplement cost saving and effective for degenerative eye disease

August 24, 2017
A supplement that combines antioxidants with zinc and copper is a relatively inexpensive and effective means of halting the progression of a certain type of degenerative eye disease, concludes research published online in ...

Researchers identify key compounds to resolve abnormal vascular growth in AMD

August 21, 2017
A compound of specific bioactive products from a major family of enzymes reduced the severity of age-related macular degeneration (AMD) in a preclinical model, according to a new study led by Massachusetts Eye and Ear researchers. ...

World's blind population to soar: study

August 3, 2017
The world's blind will increase threefold from about 36 million today to 115 million in 2050 as populations expand and individuals grow ever older, researchers said Thursday.

Simulations signal early success for fractal-based retinal implants

July 27, 2017
Computer simulations of electrical charges sent to retinal implants based on fractal geometry have University of Oregon researchers moving forward with their eyes focused on biological testing.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.