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. Here, TGFB1 is linked to CAPN5-related vitreoretinopathy.