Stem cell model of albinism to study related eye conditions
Use of patient-derived stem cells will enable high-throughput drug
screening for potential therapeutics

Date:
January 11, 2022
Source:
NIH/National Eye Institute
Summary:
Researchers have developed the first patient-derived stem cell
model for studying eye conditions related to oculocutaneous albinism
(OCA).



FULL STORY ==========================================================================
The model's development is described in the January issue of the journal
Stem Cell Reports. NEI is part of the National Institutes of Health.


========================================================================== "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, Ph.D., a staff scientist in the NEI Ophthalmic Genetics
and Visual Function Branch, and the lead author of the report.

OCA is a set of genetic conditions that affects pigmentation in the
eye, skin, and hair due to mutation in the genes crucial to melanin
pigment production. In the eye, pigment is present in the retinal
pigment epithelium (RPE), and aids vision by preventing the scattering
of light. The RPE is located right next to the eye's light-sensing photoreceptors and provides them nourishment and support. People with
OCA lack pigmented RPE and have an underdeveloped fovea, an area within
the retina that is crucial for central vision. The optic nerve carries
visual signals to the brain.

People with OCA have misrouted optic nerve fibers. Scientists think that
RPE plays a role in forming these structures and want to understand how
lack of pigment affects their development.

"Animals used to study albinism are less than ideal because they lack
foveae," said Brian P. Brooks, M.D., Ph.D., 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 make the model, researchers reprogrammed skin cells from individuals
without OCA and people with the two most common types of OCA (OCA1A
and OCA2) into pluripotent stem cells (iPSCs). The iPSCs were then differentiated to RPE cells. The RPE cells from OCA patients were
identical to RPE cells from unaffected individuals but displayed
significantly reduced pigmentation.

The researchers will use the model to study how lack of pigmentation
affects RPE physiology and function. In theory, if fovea development is dependent on RPE pigmentation, and pigmentation can be somehow improved,
vision defects associated with abnormal fovea development could be at
least partially resolved, according to Brooks.

"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 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.

========================================================================== Story Source: Materials provided by NIH/National_Eye_Institute. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Aman George, Ruchi Sharma, Tyler Pfister, Mones Abu-Asab, Nathan
Hotaling, Devika Bose, Charles DeYoung, Justin Chang, David
R. Adams, Tiziana Cogliati, Kapil Bharti, Brian P. Brooks. In
vitro disease modeling of oculocutaneous albinism type 1 and
2 using human induced pluripotent stem cell-derived retinal
pigment epithelium. Stem Cell Reports, 2022; 17 (1): 173 DOI:
10.1016/j.stemcr.2021.11.016 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220111112034.htm

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