New concepts for reconstruction of retinal and pigment epithelial tissues

Abstract

The rise of stem cell-based regenerative medicine has created great hopes for novel therapies for major blinding diseases. Intensive relevant research is grounded on a deep cellular and molecular knowledge of the complex embryonic development of the neural retina and retinal pigmented epithelium (RPE) from the eye vesicle. This research similarly relies on a long history of transdifferentiation studies, having revealed an innate capacity to regenerate a more or less complete retinal tissue from RPE. To analyze principles of self-organization that govern retinal tissue (re-)construction under normal or regenerative conditions on a ‘cell-by-cell’ basis, the reaggregate approach of dispersed embryonic progenitor cells into retinotypic cellular spheres has been instrumental. Based on this knowledge, a multitude of fascinating studies using embryonic, induced pluripotent, adult stem cells, or permanent cell lines from various species have been carried out over the past two decades, and directed production of human retinal and RPE cell types has become possible. Moreover, reconstruction of complete retinal tissue, of functioning RPE monolayers, or even eye-like structures has become feasible. After their implantation into appropriate animal models for blinding diseases, some functional recovery has been observed. Here, we review some historical, cellular and molecular perspectives of this vast research program.

Keywords::

• BMPs
• cell reaggregation
• cell specification
• eye diseases
• ocular development
• regenerative medicine
• retinal spheroids
• RPE development
• stem cells
• tissue engineering
• transdifferentiation

Acknowledgements

We thank G Bachmann, A Bytyqi, F Frohns, M Rieke, A Rothermel, L Sperling, J Steinfeld and E Willbold for documentation, secretarial support and helpful discussions.

Financial & competing interests disclosure

This work was supported by the Deutsche Forschungsgemeinschaft (DFG La 379/12-1), European Space Organisation ESA and ECSST Japan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.