Treatment can improve vision in macular degeneration

Source: Erin Silversmith, Wikimedia

 

Macular degeneration is a form of age-related blindness that develops over time. The "wet" form is caused by the growth of new blood vessels in the back of the eye, called neovascularization. The new vessels swell and leak, leading to loss of central vision. VEGF-A (vascular endothelial growth factor-A) has been found to be a key player in the process of angiogenesis, which is necessary for the new vessel growth. Treatments for macular degeneration aim at inhibiting this molecule.

Keratoprosthesis: Artificial corneas restore sight

Source: Wikimedia, Erin Silversmith

Corneal transplants have been pursued as an answer to blindness caused by problems with the clear outer layer of the eye, such as macular dystrophy. But the procedure has risk of rejection, and corneal tissue, like other transplanted tissues, is not always readily available. The solution to this has been the development of an artificial cornea.


The artificial cornea is a clear acrylic prosthesis (keratoprosthesis) implanted into the eye. A lot of work on the clinical applicability and safety of the design and procedure has been done in Boston – known as Boston Keratoprosthesis. A few other types are also commercially available for surgeons from other medical device companies. In early December 2010, one such surgery restored an Englishman’s sight. Read more about the new eye operation that restored the man's sight.

Stem cells and blindness

Can stem cells cure blindness? Possibly, according to a study in Cell Stem Cell. A group at the University of Washington has found that embryonic stem cell-derived photoreceptors injected into mice with degenerative retinas results in regenerated retinal layers and increased light response.

The Mechanism of Interest

The loss or degeneration of photoreceptors in the retina, the light sensing receptors in the eye, leads to blindness. This is the mechanism seen with age-related macular degeneration, a common age-related disease. Several approaches to replacing the photoreceptors have been attempted, but a recent study in the journal Cell Stem Cell indicates that embryonic stem cells may hold the key.

Replacing Degenerative Photoreceptors

For over a decade, several types of cells have been investigated to determine their ability to regenerate the retina, leading to disappointing results. In 1998, Takashi et al. found that hippocampus-derived neural progenitor cells from adult rats could form a uniform layer in the adult rat eye, expressing markers of developing neurons. However, the cells did not eventually express retinal neuron markers, indicating incomplete retina formation.

In 2004, Klassen et al. looked at retinal progenitor cells isolated from day-old mice and found some improvement in light-mediated behavior of adults with retinal grafts, indicating that the neurons regenerated the retina to some extent. That same year, Coles et al. looked at retinal stem cells and found that they could differentiate into retinal cells. Two years later, MacLaren et al. showed that these stem cell-derived cells could be transplanted and populate a damaged eye. Also in 2006, Lamba et al. showed that embryonic stem cells could be directed to become retinal cells, including photoreceptors expressing specific markers, something the other cell types had not achieved.

The Cell Study

Lamba, Gust, and Reh at the University of Washington used mice with a mutation in their photoreceptors that mimics the vision disorder Leber’s Congenital Amaurosis. The mutant mice were injected with the embryonic stem cell-derived retinal cells developed by Lamba et al., as were normal mice, both adult and newborn. The results were different for each group of mice, depending on their needs.

The cells regenerated the retina and photoreceptors of the mutant mice and restored the light response in these mice. In normal mice, the cells simply settled and integrated into various layers of the retina, choosing to be photoreceptors more often in the adults, but without damaging the eye. The researchers are hopeful that they have found a possible treatment for photoreceptor loss. Potentially, photoreceptors can be developed from human embryonic stem cells for cell replacement therapy.

The Future of Blindness

This recent study is but one possibility for replacing damaged cells in one tissue. There are other causes of blindness that will not be affected by this treatment. Replacing the retinal cells will not help with optic nerve disorders or damage to the occipital lobe of the brain. However, clinical trials into the use of stem cell-derived photoreceptors as cell replacement therapy in macular degeneration may help millions of people in the United States alone.

References:

Coles et al. Facile isolation and the characterization of human retinal stem cells. PNAS USA, 101, 2004.

Klassen et al. Multipotent retinal progenitors express developmental markers, differentiate into retinal neurons, and preserve light-mediated behavior. Investigative Ophthalmology and Visual Science, 45, 2004.

Lamba et al. Efficient generation of retinal progenitor cells from human embryonic stem cells. PNAS USA, 103, 2006.

Lamba, Gust, and Reh. Transplantation of human embryonic stem cell-derived photoreceptors restores some visual function in Crx-deficient mice. Cell Stem Cell, 4, 2009.

MacLaren et al. Retinal repair by transplantation of photoreceptor precursors. Nature, 444, 2006.

Takashi et al. Widespread integration and survival of adult-derived neural progenitor cells in the developing optic retina. Molecular and Cellular Neurosciences, 12, 1998.