Abstract
Presentation Description :
Oculocutaneous albinism (OCA) is a genetically heterogeneous autosomal recessive condition characterized by reduced melanin pigment in the hair, skin and eyes, as well as developmental eye abnormalities (foveal hypoplasia, ganglion cell axon misrouting) that limit vision. The reason why reduced melanin in the retinal pigment epithelium (RPE)/choroid leads to these neural retinal abnormalities is unclear, but we postulate that one or more non-cell autonomous factors from the former are influencing development in the latter. Given that foveal development continues after birth, therapeutic intervention to normalize such factors early in life could potentially improve vision in OCA patients.
To investigate the molecular pathogenesis of albinism we have created RPE derived from induced pluripotent stem cells (iPSCs) from patients with two forms of albinism—OCA1A (due to mutations in TYROSINASE) and OCA2 (due to mutations in the P gene). We will review the morphologic and functional characteristics of this model, emphasizing differences in cell-cell adhesion, apical processes, and gene expression, with particular attention to druggable targets and potential biomarkers for clinical trials.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.