Developing a Macula in Stem Cell-Derived Human Retinal Organoids

Abstract

Retinal development is a highly complex process that has been extensively studied across various animal models. With the advent of pluripotent stem cells and three-dimensional retinal organoids (hROs), we can now investigate the intricacies of human retinogenesis in vitro. However, this requires retinal organoids that faithfully replicate the structure of the human retina.

In the primate retina, an especially important and complex structure, the macula, is located at the central retina, where retinogenesis is initiated. The macula is critical because it is responsible for most of our colour vision and visual acuity, which together account for a large part of our overall sense of sight. While retinal development in model organisms has been widely investigated, the macula is unique to primates, and its development remains poorly understood due to tissue scarcity.

With the rise of in vitro hROs, we can now model many aspects of human retinal development; however, current organoid technologies lack this key macular feature.

Therefore, the overall aim of this thesis work was to generate an in vitro human macula that would enable deeper insights into macular development and facilitate the study and treatment of maculopathies such as Stargardt's disease and age-related macular degeneration (AMD). In the future, macular organoids will provide a more effective platform for cell therapy, including transplantation of cone-rich photoreceptor populations or even the creation of macular transplantation patches.