The development of the model is detailed in the journal Stem Cell Reports, which was published in January.
“This ‘disease-in-a-dish’ system will help us understand how the absence of pigment in albinism leads to abnormal development of the retina, optic nerve fibers, and other eye structures crucial for central vision,” said Aman George, PhD, a staff scientist in the NEI Ophthalmic Genetics and Visual Function Branch, and the lead author of the report.
OCA is a group of genetic disorders that impair pigmentation in the eyes, skin, and hair as a result of mutations in genes involved in the generation of melanin pigment.
Pigment is found in the retinal pigment epithelium (RPE) of the eye, and aids vision by preventing the scattering of light.
Optic nerve fibers are misrouted in patients with OCA. Scientists believe RPE is involved in the formation of these structures, and they want to know how the lack of pigment affects their development.
“Animals used to study albinism are less than ideal because they lack foveae,” said Brian P. Brooks, MD, PhD, NEI clinical director and chief of the Ophthalmic Genetics and Visual Function Branch. “A human stem cell model that mimics the disease is an important step forward in understanding albinism and testing potential therapies to treat it.”
To create the model, researchers converted skin cells from people without OCA and those with the two most common types of OCA (OCA1A and OCA2) into pluripotent stem cells (iPSCs). After that, the iPSCs were developed into RPE cells.
The RPE cells from OCA patients were identical to RPE cells from unaffected individuals but displayed significantly reduced pigmentation.
The model will be used to investigate how RPE physiology and function are affected by a lack of pigmentation. According to Dr. Brooks, vision impairments linked with abnormal fovea development could be at least partially corrected if fovea development is dependent on RPE pigmentation and pigmentation can be improved.
“Treating albinism at a very young age, perhaps even prenatally, when the eye’s structures are forming, would have the greatest chance of rescuing vision,” said Dr. Brooks. “In adults, benefits might be limited to improvements in photosensitivity, for example, but children may see more dramatic effects.”
The team is now exploring how to use their model for high-throughput screening of potential OCA therapies.