Age-related macular degeneration (AMD) is one of the leading causes of blindness among elderly. The disease has two advanced stages, the dry and the wet stage. The dry stage is trigged by the death of retinal pigment epithelium (RPE) cells followed by photoreceptor (PR) cell death and choroidal thinning. In contrast the wet-stage is characterized by overt proliferation of choroidal capillaries. It is thought that disease processes for both these advanced stages initiate in the back of the eye around the PR/RPE/choroid complex. However, due to lacking human models, the disease initiating events that lead to functional and anatomical changes in the PR/RPE/choroid complex are not well understood. We have combined bioprinting, tissue engineering, and induced pluripotent stem (iPS) cell technology to develop a 3D in vitro model of RPE/choroid. Using a collagen-based gel for encapsulation of patient-specific iPS cell-derived endothelial cells, choroidal fibroblasts, and pericytes, we successfully bioprinted a microvascular network on one side of a biodegradable scaffold. On the other side of the scaffold, we grow a RPE monolayer differentiated from the same patients iPS cells. This 3D tissue mimics the anatomy and functional properties of native RPE/choroid unit. Similar to wet-AMD, the in vitro microvascular network also proliferates in response to VEGF. This work provides a platform to discover disease initiating pathways and the possibility of identifying potential therapeutic drugs for wet-AMD. In a parallel approach, we are developing a controlled biomimetic microenvironment based microfluidic culture platform to recapitulated the human outer blood retina barrier using iPSC-derived RPE and endothelial cells. The purpose of this investigation is to serve as a groundwork for developing functional retina degenerative disease models on the microchips and improving upon the existing preclinical drug development process. We successfully designed and developed a microfluidic chip platform that facilitates seamless image acquisition, fluidic connection and disconnection, and in situ assays. Furthermore, we showed that the chip system is capable of co-culturing RPE and endothelial cells in a dual-channel microfluidic chip and the clamping platform,
| Song, Min Jae; Bharti, Kapil (2016) Looking into the future: Using induced pluripotent stem cells to build two and three dimensional ocular tissue for cell therapy and disease modeling. Brain Res 1638:2-14 |
