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Stem cell therapy for macular degeneration is an emerging treatment approach aimed at restoring vision in individuals suffering from various forms of macular degeneration, particularly age-related macular degeneration (AMD).^[1] This therapy involves the transplantation of stem cells into the retina to replace damaged or lost retinal pigment epithelium (RPE) and photoreceptor cells, which are critical for central vision. Clinical trials have shown promise in stabilizing or improving visual function, but are nevertheless inefficient.^[2]

History

The first fetal retinal transplant into the anterior chamber of animal eyes was reported in 1959. In 1980, experiments involving cell cultures of retinal pigment epithelium (RPE) began. Human RPE cells grown in culture were subsequently transplanted into animal eyes, initially using open techniques and later through closed cavity vitrectomy methods.^[1]

In 1991, Gholam Peyman attempted to transplant RPE in humans, but the success rate was limited. Later efforts focused on allogenic fetal RPE cell transplantation, which faced significant challenges due to immune rejection. It was observed that rejection rates were lower in cases of dry age-related macular degeneration (AMD) compared to the wet form of the disease. Autologous RPE transplantation became more common, using two main techniques: RPE suspension and full-thickness RPE-choroid transplantation. Clinical outcomes from autologous RPE-choroid transplantation, where tissue from the eye’s periphery is transplanted to a diseased area, have shown promise.^[3]

Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. Sheets of retinal cells used in these procedures were initially harvested from aborted fetuses, which raised ethical concerns for some. These retinal sheets, when transplanted over damaged corneas, stimulated repair and eventually restored vision.^[4]^[5] In June 2005, a team led by Sheraz Daya at Queen Victoria Hospital in Sussex, England, restored sight in forty patients using a similar technique with adult stem cells sourced from the patient, a relative, or a cadaver.^[6]

In 2014, surgeons at Riken Institute’s Center for Developmental Biology reported the first transplantation of induced pluripotent stem cells (iPSCs) into a human patient. This clinical study involved creating a retinal sheet from iPSCs, developed by Shinya Yamanaka, which were reprogrammed from the patient's own mature cells. The retinal sheet was transplanted into a woman in her 70s suffering from age-related macular degeneration (AMD), a condition that blurs central vision and can lead to blindness. The use of iPSCs aimed to halt the progression of AMD. In March 2017, the team conducted the first successful transplant of retinal cells created from donor-derived iPSCs into a patient with advanced wet AMD. This surgery was made more efficient by using "super donor" cells, derived from individuals with specific white blood cell types that reduce the risk of immune rejection. Approximately 250,000 retinal pigment epithelial cells, generated from these donor-derived iPSCs, were transplanted into the patient’s eye.^[7]