The Cytoskeleton of the Retinal Pigment Epithelium: from Normal Aging to Age-Related Macular Degeneration

Abstract

The retinal pigment epithelium (RPE) is a unique epithelium, with major roles which are essential in the visual cycle and homeostasis of the outer retina. The RPE is a monolayer of polygonal and pigmented cells strategically placed between the neuroretina and Bruch membrane, adjacent to the fenestrated capillaries of the choriocapillaris. It shows strong apical (towards photoreceptors) to basal/basolateral (towards Bruch membrane) polarization. Multiple functions are bound to a complex structure of highly organized and polarized intracellular components: the cytoskeleton. A strong connection between the intracellular cytoskeleton and extracellular matrix is indispensable to maintaining the function of the RPE and thus, the photoreceptors. Impairments of these intracellular structures and the regular architecture they maintain often result in a disrupted cytoskeleton, which can be found in many retinal diseases, including age-related macular degeneration (AMD). This review article will give an overview of current knowledge on the molecules and proteins involved in cytoskeleton formation in cells, including RPE and how the cytoskeleton is affected under stress conditions—especially in AMD.

Polarity and epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy

“…The two extracellular loops of occludin mediate adhesion of adjacent cells and block the movement of plasma components. The C-terminal domain combines directly with ZOs, subsequently interacting with the actin cytoskeleton, which is essential to organizing and maintaining cell polarization ( Balda & Matter, 2016 ; Furuse et al, 1994 ; Shin, Fogg & Margolis, 2006 ; Tarau et al, 2019 ). Feng et al (2019) demonstrated that during EMT, the breakdown of TJs resulting from loss of claudin-1 causes ARPE-19 cells to lose their epithelial phenotype and transform into fibroblasts, promoting the development of PVR.…”

Reproducible production and image-based quality evaluation of retinal pigment epithelium sheets from human induced pluripotent stem cells

“…Normal polarized RPE cells possess F-actin in the transcellular membrane microvilli, circumferential microfilament bundles, and basal infolding 49 . However, accumulating evidence has demonstrated irregular distribution of F-actin in aged human RPE and the RPE of AMD patients 50 . The cytoskeleton has also been shown to affect the distribution of apical surface area in epithelial sheets 51 .…”

Peer Review #1 of "Polarity and epithelial-mesenchymal transition of retinal pigment epithelial cells in proliferative vitreoretinopathy (v0.1)"

“…The two extracellular loops of occludin mediate adhesion of adjacent cells and block the movement of plasma components. The C-terminal domain combines directly with ZOs, subsequently interacting with the actin cytoskeleton, which is essential to organizing and maintaining cell polarization (Balda & Matter 2016;Furuse et al 1994;Shin et al 2006;Tarau et al 2019). Feng et al (2019) demonstrated that during EMT, the breakdown of TJs resulting from loss of claudin-1 causes ARPE-19 cells to lose their epithelial phenotype and transform into fibroblasts, promoting the development of PVR.…”