Macular Degeneration: Preserving Eyesight Through Regeneration Science

New sight for those who are blinded by macular degeneration may be moving closer to the list of medical miracles. In the young field of regenerative medicine, a UCSF scientist has invented unique microscopic scaffolds to support the growth of new cells to replace those lost to disease. By Rachel Tompa Macular degeneration is the major cause of vision loss in the United States. The disease, which kills photoreceptors that convey visual signals from the eye to the brain, often strikes the elderly. Its defining symptom is blurriness in the central visual field, a blurriness that robs many people of their ability to drive or read. An estimated 10 million Americans already suffer from age-related macular degeneration. And as the aging population continues to increase, so too will cases of blindness associated with the disease. Current treatments can stop or slow destruction of the photoreceptors, but there are no proven strategies to restore lost vision. Put simply, when the photoreceptors die, new cells do not arise to take their place. UCSF's Sarah Tao, PhD, a postdoctoral scientist who works in the bioengineering laboratory of Professor Tejal Desai, PhD, hopes to counteract the slide toward blindness with a new approach that capitalizes on the ability of stem cells to regenerate photoreceptors. In short, Tao has developed a scaffold - with key features fabricated on a microscopic scale - to guide cells as they grow and help them survive. Stem Cells and Scaffolds Stem cells in the retina can give rise to any of the several retinal cell types, including two types of photoreceptors known as rods and cones. Earlier experiments intended to restore vision to blind rodents failed when either retinal stem cells or their first-generation descendents, called progenitors, were injected into the eye. The cells were unable to network successfully within the eye and perform their necessary roles, and they eventually died. Normally during early development, stems cells growing within the milieu of cells destined to become the eye detect and respond to chemical and physical cues from surrounding tissue. The cues tell cells where to go and when to increase their numbers, and help determine the specialization of progeny cells. Scientists do not know what all the cues are, or which ones are lost after early development is complete. The biomimetic scaffolds developed by Tao substitute in part for the guidance provided naturally by these cues during early development. The scaffolds hold stem cells in place and more accurately guide them as they go through the long process of developing into working photoreceptors. Guiding immature stem cells to grow in the proper location within the retina is not sufficient to recreate the complex architecture of the adult retina. Photoreceptors also have to develop specialized extensions that contact other cells in the eye and the central nervous system. With the scaffolds, Tao aims to provide a structure to hold stem cells in the proper orientation to make these connections and to seamlessly integrate the cells into the retina. From Microtechnology to Nanotechnology Tao uses specialized equipment in the California Institute for Quantitative Biomedical Research (QB3) Biomedical Micro and Nanofabrication Center at UCSF to construct scaffolds - thin discs of biodegradable polymer. The flexible scaffold is designed to sit snugly against the mouse's retina and hold the stem cells in place as they develop. The scaffolds are one millimeter in diameter, but only six micrometers thick - thinner than the width of most mammalian cells. The scaffolds have small, evenly spaced pores where the stem cells sit. Once a scaffold is loaded with immature stem cells, Tao surgically introduces it into the eye. So far, Tao has tested her scaffolds exclusively on mice. Tao hopes to apply even smaller and more delicate construction techniques to her scaffolds, with fabrications on the nano scale - a nanometer being 1,000 times smaller than a micrometer. Combining micro- and nanotechnology would allow Tao to create another level of organization to better guide the extensions of the developing stem cells as they make their connections with other cells in the eye or brain. "To be able to control cells at that sort of scale," Tao says, "is mind-boggling." Tao has begun testing her scaffolds in collaboration with Michael Young, an assistant professor at Harvard University. They have surgically implanted scaffolds seeded with retinal stem cells into mice. By fluorescently labeling the stem cells before implantation, they can track their growth and orientation in the mouse's eye. Cells delivered using Tao's scaffolds have been able to integrate into the mouse's retina and to begin developing into different cell types. The next step is to use Tao's scaffolds to try to restore vision in blind mice. Ultimately, Tao's scaffolds may lead to new treatment strategies to reverse macular degeneration and related eye diseases in humans. Photo/Majed Related Links: Therapeutic Micro and Nanotechnology Laboratory (Desai Laboratory) California Institute for Quantitative Biomedical Research (QB3) advancing health worldwide™ website