Stem cell therapy holds promise

New York-Stem cell-based therapy is an important potential treatment to restore vision in patients with a wide range of retina disease, said Lucian V. Del Priore, MD, PhD.

"Stem cell replacement strategies have the potential to improve vision in patients previously considered untreatable. Retinal degenerations are the leading cause of blindness in the world," said Dr. Del Priore, professor, Department of Ophthalmology, and director of the Bruch's Membrane Laboratory, Columbia University College of Physicians and Surgeons, New York.

Retinal degenerations are a very heterogeneous group of disorders, he said.

Peripheral retinal degenerations

Dr. Del Priore's goal is to use stem cell transplantation to treat peripheral retinal degenerations, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).

According to Dr. Del Priore, the eye is an excellent target organ for stem cell therapy for many reasons. First, refinement of surgical instrumentation allows cellular and subcellular scale tissue manipulations (1 to 20 µm). Local delivery of cells into well-defined spaces is possible, and only small numbers of cells delivered to a precise area within the retina will be needed. Determining the efficacy of therapy is important. Here, ophthalmologists have a distinct advantage compared with other stem cell scientists, since other areas of the same eye can serve as a control.

The fact that retinal degenerations are well-characterized, and excellent function testing of the eyes is available-including visual fields, multifocal electroretinogram, and microperimetry-also make the eye an excellent target for stem cell therapy. In addition, multiple imaging modalities are possible to follow the fate of transplanted cells, including with fundus photography, autofluorescence imaging, fluorescein angiography, and optical coherence tomography, which provides the equivalent of in vivo histologic sections, he explained.

Stem cell transplants can survive, migrate, differentiate, and integrate within the retina in small numbers, according to recent research. Various stem cells have been studied, including embryonic, neural, mesenchymal, retinal, and adult stem cells. They have been shown to be remarkably adaptable, with the capacity to adopt retina-like morphologies and phenotypes.

Dr. Del Priore and fellow researchers have induced human embryonic stem cells (hESCs) to differentiate into retinal pigment epithelium (RPE) or neural retinal cells by seeding the hESCs onto human Bruch's membrane explants. Collaborator Stephen Tsang, MD, PhD, has demonstrated the efficacy of hESC-derived RPE in rescuing function in an animal model of retinal degenerations. Additional studies are being performed to isolate tissue-specific stem cells from the eye, and to investigate the efficacy of transplanting tissue-specific and differentiated hESCs into animal models of retinal degenerations.