Retinogenesis of the Human Fetal Retina: An Apical Polarity Perspective

Abstract

The Crumbs complex has prominent roles in the control of apical cell polarity, in the coupling of cell density sensing to downstream cell signaling pathways, and in regulating junctional structures and cell adhesion. The Crumbs complex acts as a conductor orchestrating multiple downstream signaling pathways in epithelial and neuronal tissue development. These pathways lead to the regulation of cell size, cell fate, cell self-renewal, proliferation, differentiation, migration, mitosis, and apoptosis. In retinogenesis, these are all pivotal processes with important roles for the Crumbs complex to maintain proper spatiotemporal cell processes. Loss of Crumbs function in the retina results in loss of the stratified appearance resulting in retinal degeneration and loss of visual function. In this review, we begin by discussing the physiology of vision. We continue by outlining the processes of retinogenesis and how well this is recapitulated between the human fetal retina and human embryonic stem cell (ESC) or induced pluripotent stem cell (iPSC)-derived retinal organoids. Additionally, we discuss the functionality of in utero and preterm human fetal retina and the current level of functionality as detected in human stem cell-derived organoids. We discuss the roles of apical-basal cell polarity in retinogenesis with a focus on Leber congenital amaurosis which leads to blindness shortly after birth. Finally, we discuss Crumbs homolog (CRB)-based gene augmentation.

Mouse Models of Inherited Retinal Degeneration with Photoreceptor Cell Loss

“…A primary defect of a disruption in CRB1 is the fragmentation of the outer limiting membrane [345,346]. As reviewed previously [344,347], the outer limiting membrane consists of adherens/tight junctions formed in part by the CRB1 complexes between Müller glia and the rod or cone IS that form a diffusion barrier. Loss of components of the CRB1 complexes (CRB1-MPP5-PATJ, CRB1-MPP5-MPDZ, and CRB1-PARD6A-MPP5-MPP3/MPP4) leads to lamination defects with formation of rosettes and a progressive loss of PRs.…”

The Neuroprotective Effect of Tea Polyphenols on the Regulation of Intestinal Flora

“…The activation of PKC in neurons is the premise of playing some neuroprotective roles [ 100 ]. In this regard, the activation of PKC by EGCG protects SH-SY5Y cells and PC12 cells from cell death induced by 6-hydroxydopamine and Aβ [ 101 ]. It was found that after taking EGCG (2 mg/kg) for 2 weeks, PKCα in the striatum of mice was significantly upregulated [ 102 ], and PKCα in the hippocampal membrane and cytoplasmic part of mice was increased [ 103 ].…”

Features of Retinal Neurogenesis as a Key Factor of Age-Related Neurodegeneration: Myth or Reality?

“…The bulk of highly complex retinal development occurs between gestational week 24 and the age of 3 to 4 months, when the optic nerve becomes fully myelinated [58]. Retinogenesis in humans and structural formation of all the retinal layers take place during fetal development [59]. The peripheral retina of humans shares laminated cellular organization and basic developmental events with that of other vertebrates [57].…”