Effect of hrWnt7a on Human Retinal Pigment Epithelial Cells In Vitro

Abstract

Human recombinant protein Wnt7a (hrWnt7a) inhibits cell proliferative activity and triggers cell polarization. Although cell polarization process was maintained only over a short time, probably via microenvironmental stimuli, hrWnt7a is involved in the transformation of the retinal pigment epithelium. Analysis of Wnt signaling pathway and its regulation will help to understand the processes in retinal pigment epithelial cells under pathological conditions, which can be useful in developing new generation drugs.

Reprogramming of Differentiated Mammalian and Human Retinal Pigment Epithelium: Current Achievements and Prospects

“…In cell culture, RPE cells lose their original features, such as pigmentation, significantly reduce the expression of specific markers RPE65, MITF, and CRALBP and acquire features of neural cells on markers MUSASHI1, NESTIN, βIII-TUBULIN, GFAP, DOUBLECORTIN, and NF 68 and 200 kDa. Our studies also demonstrate that RPE cells of the human embryo and adult in vitro in media with the addition of morphogens and growth factors lose their pigment granules, dedifferentiate, proliferate, and exhibit markers of several types of neural and glial cells (Milyushina et al, 2009(Milyushina et al, , 2011(Milyushina et al, , 2012Kuznetsova et al, 2014;Kuznetsova et al, 2015Kuznetsova et al, , 2019. At the dedifferentiation stage, cells acquire stem/neuroepithelial cell traits by expressing OCT4, NANOG, KLF4, OTX2, PAX6, and NESTIN (Milyushina et al, 2009Kuznetsova et al, 2014Kuznetsova et al, , 2015Kuznetsova et al, , 2019aKuznetsova et al, , 2019b.…”

“…Our studies also demonstrate that RPE cells of the human embryo and adult in vitro in media with the addition of morphogens and growth factors lose their pigment granules, dedifferentiate, proliferate, and exhibit markers of several types of neural and glial cells (Milyushina et al, 2009(Milyushina et al, , 2011(Milyushina et al, , 2012Kuznetsova et al, 2014;Kuznetsova et al, 2015Kuznetsova et al, , 2019. At the dedifferentiation stage, cells acquire stem/neuroepithelial cell traits by expressing OCT4, NANOG, KLF4, OTX2, PAX6, and NESTIN (Milyushina et al, 2009Kuznetsova et al, 2014Kuznetsova et al, , 2015Kuznetsova et al, , 2019aKuznetsova et al, , 2019b. Although mRNA expression of pluripotency marker genes is very low compared to human iPSCs (Kuznetsova et al, 2019), the activity of these genes indicates that they can act as pioneer factors (Kuzmich et al, 2015).…”