Table 1 Most frequent chemical molecules used for iPSCs differentiation toward RPEs

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]