Table 1.

Most frequent chemical molecules used for iPSCs differentiation toward RPEs

Chemical molecule	Role	References
Dkk-1 or XAV939	WNT signaling inhibitor, inhibits TNKS1 and TNKS2 Initiator of lens development	[12, 45, 46]
Noggin or dorsomorphin	Bone morphogenetic protein (BMP) inhibitor, AMPK pathway inhibitor, that inhibit ALK2, ALK3, and, ALK6 Induced neural fate during embryonic development from ectoderm	[13, 45, 46, 53]
Lefty-A	Transforming growth factor beta (TGF-b) ligand	[13, 45, 46, 53]
Insulin growth factor-1 (IGF-1)	Activate IGF-1 signaling receptor Stimulate increased phosphorylation in the MAPK/ERK and PI3K/AKT signaling pathways. Regulate proliferation and differentiation of RPCs	[13, 45, 46, 53]
Activin A	Expressed in neural retina, RPE during development by expression of MITF	[13, 45, 46, 53]
Nicotinamide (vitamin B3)	Inhibitor of poly-ADP ribose polymerase (PARP)	[13, 53, 64]
SB431542	Inhibitor of the TGF-β/Activin/NODAL pathway	[64, 65]
Heparin	Modulate WNT and Shh signaling pathways	[46]
CHIR99021	GSK3β inhibitor	[53, 54]
VIP (vasoactive intestinal peptide)	Activating pp60(c-SRC) and increasing intracellular cAMP	[13]
Y-27632	Inhibitor of Rho-associated protein kinase (ROCK) signaling pathways	[11]
CKI-7	Inhibitor of casein kinase 1 (CK1)	[56]
Retinoic acid (Vitamin A)	Regulate activities of nonsteroid hormone receptors such as RARα/β/γ and RXRα/β/γ in neuroretina, RPE, periocular mesenchyme, lens, cornea, iris/ciliary body, choroid, sclera, and conjunctiva	[45]
Sonic hedgehog (Shh)	Cause cell growth, cell specialization, and normal shaping; it also activates VAX1, VAX2, and PAX2 to establish both proximal–distal and dorsal–ventral axes	[46]
LDN193189	Inhibitor of BMP pathway by inhibition of ALK1, ALK2, ALK3, and ALK6	[11]
A-83-01	Inhibitor of TGFβ kinase/activin receptor-like kinase (ALK 5)	[11]
IWR-1-endo	Inhibitor of WNT pathway; AXIN2 stabilizer	[11]
SU5402	Inhibitor of MEK/ERK pathway, VEGFR2, FGFR1, and PDGFRB	[11]