Purchase this article with an account.
Yangzi Isabel Tian, Yubing Xie; Bioengineer Functional 3D Human Retina for Understanding Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4162.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Progressive deterioration of retinal pigment epithelial (RPE) cells in elderly individuals promotes a cascade of inflammatory events that damages the retina and result in blindness-causing diseases such as age-related macular degeneration (AMD). Understanding the development of diseased retinal epithelium is critical for the treatment of degenerative eye diseases. However, much of our understanding of the metabolic and phagocytic activities that underlie a healthy, functional retinal epithelium has been gathered from in vitro 2D cell cultures, which do not faithfully recapitulate the human retina architecture and function. Recent advancement in 3D bioprinting and nanofabrication technologies offer tools to create in vivo-like tissue complex. To accurately capture the physiological behavior of RPE cells in vivo, three-dimensional (3D) extracellular environment is needed to overcome limitations of the conventional cell culture.
To reproduce the groove-like geometry of the retina, a 3D printer (BotFactory Replicator 2X) will be used to fabricate a concave, hollow semi-sphere with a diameter of 24 mm and base curvature of approximately 150 degrees, similar to dimensions of human retina. After sterilizing, the scaffold is coated with a selection of FDA-approved natural polymers to support the adhesion and expansion of human retina pigment epithelium stem cells (hRPESC). The formation of an effective blood-retinal barrier is confirmed by examining its transepithelial permeability (or electrical resistance), polarization of membrane domain and distribution of tight junction proteins on RPE cell surface.
The result shows the feasibility of culturing hRPESC on our 3D-printed, concave surface to mimic the porous micro-architecture of the native Bruch’s Membrane. We were able to recreate the continuous monolayer of mature RPE cells after 4 weeks in culture. The cells maintained the expression of their cell type specific and functional markers.
Controlling the spatial organization and behavior of RPE cells is an important step in understanding behavior of retinal epithelium and modeling disease processes in vitro. Using the 3D printed platform will advance our understanding of retinal morphogenesis, function and the ability to model of disease processes in vitro.
This PDF is available to Subscribers Only