In fact, in addition to conventional 2D planar culture, the use of 3D spheroid culture facilitates a better understanding of molecular mechanisms of TGF-β isoforms and/or hypoxia-induced effects not only on physiological states of the RPE monolayer but also pathogenic states of multiple layers observed in proliferative vitreoretinopathy as well as CNV in ARMD. The gene discussed is TGFB1; the disease is age-related macular degeneration.