Milestone in Stem Cell Transplant Therapy for Advanced Age-Related Macular Degeneration

The advanced stage of the dry form of age-related macular degeneration (AMD) is one of the chief causes of blindness in the Western world. At this stage, dry AMD causes photoreceptor cells in the retina to degenerate, which results in patches throughout the retina that are missing photoreceptor cells. This degenerative process is termed geographic atrophy, or GA.

Photoreceptor cells form the retinal layers that gather light and send images to the brain. Once they are lost, the eye cannot replace them. Areas of missing photoreceptor cells in the retina cause a black spot to appear in the visual field. In advanced dry AMD, this vision-destroying degenerative process typically progresses relentlessly through the central macula, which detects fine details, and causes significant impairment of vision and quality of life.

Although GA has no treatment, a number of promising approaches are being developed. One is the transplantation into the retina of retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESC).

Like loss of photoreceptor cells, loss of RPE cells leads to vision loss in advanced AMD. RPE cells lie in a layer just outside the retina and have many important functions that support photoreceptor cells. This week, Sandra Petrus-Reurer, a PhD candidate at the Karolinska Institutet, Stockholm, Sweden, reported the first evidence in a large-eye animal model of GA that, once hESC-derived RPE cells are transplanted, they can integrate within the recipient eye and engage in important functions that support photoreceptor cells.

For instance, the Karolinska team found that the transplanted RPE cells could continue to rescue photoreceptor cells for as long as 8 months. These results were reported at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting in Seattle, WA, on May 3, 2016, and were also published in an abstract included in the ARVO proceedings.

The researchers chose rabbits for their animal model because rabbit eyes are so similar to the human eye. And because they used albinos, which lack eye pigment, they were able to easily see that the hESC-RPE cells had integrated properly into the recipient eyes 1 week after transplantation.

To grow enough cells for transplant, the team used a two-month-long process that began with manual dissection of human embryos. The researchers cultured the cells they collected on laminin matrices associated with Bruch’s membrane and identified one laminin, LN521, that the cells grew particularly well on. After analyzing the cells, the team transplanted them and checked their function in vivo by using immunohistochemistry and real-time high-rez imaging.

At ARVO, Petrus-Reurer said that, even though the rabbit’s inner retinas were irreversibly damaged to model GA, the injected cells preserved the outer retina from damage. And the cells’ ability to integrate in patches that can cover a large area makes this approach “very powerful.” She concluded that “the derived retina cells could be used as a safe, efficient, and minimally invasive approach to treat patients suffering from advanced dry AMD.”