Stem Cell RPE Model for Oculocutaneous Albinism

Article: NIH researchers develop first stem cell model of albinism to study related eye conditions
Source: National Eye Institute
Published: January 11, 2022

RPE derived from OCA1A and OCA2 patients exhibits melanosome defects

Oculocutaneous albinism (OCA) is the absence of pigment in the eye, skin, and hair due to mutations to genes that produce the pigment melanin. A genetic disorder of autosomal recessive inheritance, OCA has seven types classified. Where albinism affects the eyes, there is a lack of pigment in the otherwise retinal pigmented epithelium (RPE) of the retina, as well as an underdeveloped fovea (foveal hypoplasia), the centermost part of the macula responsible for visual acuity. OCA also leads to abnormal decussation of optic nerve fibers connecting the eyes to the brain. Senior researcher of the project explains, "Animals used to study albinism are less than ideal because they lack foveae...A human stem cell model that mimics the disease is an important step forward in understanding albinism and testing potential therapies to treat it." The scientists used skin cells from people without OCA and from people with the two most common types of OCA (OCA1A and OCA2) and reprogrammed them into pluripotent stem cells (iPSCs), which were then differentiated into RPE cells. The researchers report that their RPE model "recapitulates the pigmentation defects seen in albinism, while retaining the apical-basal polarity and normal polygonal morphology of the constituent RPE cells." They plan to use the stem cell RPE model to study how lack of pigmentation affects RPE physiology and function, with particular attention to how RPE pigmentation affects fovea development. If there is a connection, they hope that improvement of RPE pigmentation, such as prenatally, could perhaps prevent or rescue visual deficits due to foveal hypoplasia. The team will next use their "disease in a dish" model for high-throughput screening of potential OCA therapies.

My rating of this study: ⭐⭐⭐

George A, Sharma R, Pfister T, et al. "In vitro disease modeling of oculocutaneous albinism type 1 and 2 using human induced pluripotent stem cell-derived retinal pigment epithelium." Stem Cell Reports.  17(1): P173-186. 11 January 2022. https://doi.org/10.1016/j.stemcr.2021.11.016