Newly-Discovered Corneal Stem Cells Could Be a Potential Source for Treatment of Retinal Disease

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New research from the United Kingdom has demonstrated that stem cells found in the cornea could provide a source of photoreceptor cells for transplant in persons with degenerative retinal conditions, such as age-related macular degeneration or retinitis pigmentosa.

Please note: This "proof of concept" research is in its earliest stages and has been conducted only with laboratory mice. Human clinical trials using corneal stem cells will likely not begin until 2019 or 2020, at minimum.

The research, entitled Adult Limbal Neurosphere Cells: A Potential Autologous Cell Resource for Retinal Cell Generation (terminology explained below), was published in the October 1, 2014 issue of PLoS ONE, an international, peer-reviewed, open-access online journal, published monthly by the Public Library of Science (PLoS). The PLoS is a non-profit organization of scientists and physicians who are committed to making the world's scientific and medical literature a freely available public resource.

The authors are Xiaoli Chen, Heather Thomson, Jessica Cooke, Jennifer Scott, Parwez Hossain, and Andrew Lotery, who represent the following United Kingdom-based institutions: University of Southampton, Southampton General Hospital; University of Bristol, Bristol Eye Hospital; and University Hospital Southampton NHS Foundation Trust.

Some Definitions of Terminology

  • "Limbal" or limbus: a transitional zone, about 1-2 mm wide, where the cornea joins the sclera (the "white of the eye"); the junction of the cornea and sclera
  • Cornea: a transparent dome-shaped tissue that forms the front surface of the eye; functions as a window that allows light to enter the eye.
  • Sclera: a tough white outer coating of fibrous tissue that covers the entire eyeball, except for the cornea. The muscles that move the eye are attached to the sclera.
  • Photoreceptors: retinal cells that convert light into electrical impulses for transmission of images to the brain
side view diagram of the eye

Diagram of the eye, viewed from the side
Source: National Institutes of Health

  • Neurosphere: a culture system composed of clusters of neural [i.e., nervous system] stem cells. Since neural stem cells cannot be studied in vivo [i.e., within a living organism], neurospheres provide a method to investigate neural cells in vitro [i.e., in a test tube or culture dish, typically in a laboratory].
  • Autologous: Cells or tissues derived from the same individual; one individual is both donor and recipient.

About the Research

From Corneal stem cells a potential source for retinal transplant, via Optometry Today:

Researchers at the University of Southampton discovered that stem cells taken from the corneal limbus, at the junction of the cornea and the sclera, can be programmed to form photoreceptors.

According to Andrew Lotery, Professor of Ophthalmology at the University of Southampton who led the research, "These cells are available throughout life and we hope eventually that they would be useful for retinal transplantation to repair disease, to be used in cell therapies for diseases that involve retinal degeneration, such as macular degeneration or retinitis pigmentosa."

Previous work by the team had shown that the stem cells, called limbal neurosphere cells (LNC), could be extracted from the cornea and cultured in the lab to form neurons.

In the latest experiments, LNCs taken from the corneas of mice were grown with developing retina cells in the lab, and developed themselves into retinal cells. The team also showed that when LNCs were implanted into the retinas of mice, they [developed] key characteristics of retinal cells.

While researchers are trying to find new sources of stem cells for retinal transplantation, there are pros and cons to each source.

Embryonic stem cells (ESCs), which can form any cell type in the body, are in short supply and due to their origins, have many ethical issues attached. Induced pluripotent stem cells (iPSC), which are reprogrammed adult cells, require chemicals to reprogram the cells, which have the potential to cause tumors.

"[LNCs] are another possible source of stem cells that would be taken from an accessible site and, because they are taken from the patient, they wouldn’t be at risk of rejecting the cells. These are the things that we think make it worth exploring as a source of cells for, hopefully, retinal transplantation," said Professor Lotery.

The team are now hoping to carry out further research, including tweaking the conditions needed for human cells.

More about the Study from PLoS

From the article Introduction and Discussion:

Retinal diseases are the leading cause of untreatable blindness worldwide. These conditions include age related macular degeneration (AMD) and a wide spectrum of inherited retinal diseases. Irreversible visual impairment arises due to a gradual loss of light sensory neurons – photoreceptors and/or their supportive cells the retinal pigment epithelium (RPE).

Unlike lower vertebrates, adult mammals cannot regenerate retinal neurons. The visual disability caused by these diseases carries a formidable clinical and socio-economic burden in western countries.

Cell-based therapies are an attractive approach to treat retinal disease. They offer the potential to restore functional vision. Recent studies have demonstrated that transplanted photoreceptor progenitor [i.e., "parent" or originating] cells can form … connections with the host retina and improve visual function in animal models of retinal degeneration.

Identifying practical cell sources to generate sufficient functional cells for transplantation remains challenging, however. Utilizing embryonic or fetal tissue is difficult due to limited resources, ethical issues, or risks of tumor formation. In addition, transplant rejection may occur due to chronic immune responses…. Therefore, immune-matched autologous cell resources [i.e., one individual as both donor and recipient] have considerable advantages.

… In summary, this data demonstrates the potential of mouse and human limbal neurosphere cells (LNS) to differentiate into retinal lineages in vitro [i.e., in the laboratory] and in vivo [i.e., within a living organism]. The regulation of human LNS differentiation … appears more comprehensive than with mouse LNS cells.

As a readily accessible progenitor [i.e., the "parent" or originating] cell resource that can be derived from individuals up to 97 years of age, limbal neurosphere cells remain an attractive cell resource for the development of novel therapeutic approaches for degenerative retinal diseases.

About Clinical Trials

Most clinical trials are designated as Phase I, II, or III, based on the questions the study is seeking to answer:

  • In Phase I clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe and effective dosage range, and identify possible side effects.
  • In Phase II clinical trials, the study drug or treatment is given to a larger group of people (100-300) to determine if it is effective and to further evaluate its safety.
  • In Phase III studies, the study drug or treatment is given to even larger groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
  • In Phase IV studies, after the United States Food and Drug Administration (FDA) has approved the drug, continuing studies will determine additional information, such as the drug's risks, side effects, benefits, and optimal use.

VisionAware will provide updates on this important stem cell research as they become available.

Additional Information about Stem Cell Research


Topics:
Low Vision
In the News
Medical Updates
Macular Degeneration
Retinitis Pigmentosa
There are currently 2 comments

Re: Newly-Discovered Corneal Stem Cells Could Be a Potential Source for Treatment of Retinal Disease



You rarely comment on Juvenile Retinoschisis treatment and research - but I'm wondering if this might be included? Thanks I appreciate any info you can give me. I scan your articles HOPING but don't see much being done for this particular genetic disease treatment.


Re: Newly-Discovered Corneal Stem Cells Could Be a Potential Source for Treatment of Retinal Disease



Hello kcsummer:

First, I apologize for not replying sooner. Somehow, I missed your comment.

I wish I could report more on juvenile retinoschisis, too. My best source for ongoing genetic research is the Foundation Fighting Blindness. I visited their website today and read this:

A Canadian researcher, Dr. Robert Molday (http://biochem.ubc.ca/person/robert-molday), is a world leader in research on juvenile retinoschisis. He has been funded by the Foundation Fighting Blindness to study this disease, and he currently leads an international team of researchers funded by the Foundation Fighting Blindness and the Canadian Institutes of Health Research, which aims to develop gene treatments for several genetic conditions – including retinoschisis.

I hope this is helpful.
Maureen


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