Abstract

Millions of adults are affected by progressive vision loss worldwide. The rising incidence of retinal diseases can be attributed to damage or degeneration of neurons that convert light into electrical signals for vision. Contemporary cell replacement therapies have transplanted stem and progenitor-like cells (SCs) into adult retinal tissue to replace damaged neurons and restore the visual neural network. However, the inability of SCs to migrate to targeted areas remains a fundamental challenge. Current bioengineering projects aim to integrate microfluidic technologies with organotypic cultures to examine SC behaviors within biomimetic environments. The application of neural phantoms, or eye facsimiles, in such systems will greatly aid the study of SC migratory behaviors in 3D. This project developed a bioengineering system, called the μ-Eye, to stimulate and examine the migration of retinal SCs within eye facsimiles using external chemical and electrical stimuli. Results illustrate that the imposed fields stimulated large, directional SC migration into eye facsimiles, and that electro-chemotactic stimuli produced significantly larger increases in cell migration than the individual stimuli combined. These findings highlight the significance of microfluidic systems in the development of approaches that apply external fields for neural repair and promote migration-targeted strategies for retinal cell replacement therapy.

Highlights

  • An unprecedented 500 million adults, worldwide, will be visually impaired by the year2050 [1]

  • Photoreceptor neurons of the outer nuclear layer (ONL) absorb and transduce light into electrical signals via the processes of phototransduction. These signals are transmitted across different neuronal groups in the inner nuclear layer (INL) and ganglion cell layer (GCL) to produce images of objects in the brain

  • Eye facsimiles were synthesized from alginate, a hydrogel used in ophthalmology to provide controlled chemical release within biomimetic environments (Figure 3) [74]

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Summary

Introduction

An unprecedented 500 million adults, worldwide, will be visually impaired by the year2050 [1]. Vision loss in mature and aging adults is prevalent in developed countries [2–4]. Photoreceptor neurons of the outer nuclear layer (ONL) absorb and transduce light into electrical signals via the processes of phototransduction. These signals are transmitted across different neuronal groups in the inner nuclear layer (INL) and ganglion cell layer (GCL) to produce images of objects in the brain. Since retinal neurons cannot self-repair, cell damage rapidly propagates synaptic dysfunction [7,8] to result in progressive vision loss from complex disorders, such as age-related macular degeneration [9,10], diabetic retinopathy [11], and retinitis pigmentosa [12]

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