Altered transcriptome and disease-related phenotype emerge only after fibroblasts harvested from patients with age-related macular degeneration are differentiated into retinal pigment epithelium.

摘要: Abstract We have reported previously that retinal pigment epithelium (RPE) differentiated from induced pluripotent stem cells (iPSC) generated fibroblasts of patients with age-related macular degeneration (AMD) exhibit a degenerative disease phenotype and distinct transcriptome compared to age-matched controls. Since the genetic composition iPSC RPE are inherited fibroblasts, we investigated whether differential behavior was present in parental prior differentiation cell lines into RPE. Principal component analyses revealed significant overlap (essentially no differences) between AMD After reprogramming, there difference versus normal donors. In contrast, derived segregated two clusters AMD-derived Interestingly, mitochondrial dysfunction evident after approximately months culture. Moreover, these differences were not iPSC. This study demonstrates an altered impaired function controls, original or These results suggest pathology is triggered upon parent More this phenomenon could advance current understandings etiology development novel therapeutic targets.