We’re meeting the challenge of degenerative eye diseases

Ex vivo

Our ex vivo approach begins with pluripotent stem cells, which have the potential to differentiate into any cell type and directs their differentiation into any of several specific ocular cell lineages. These differentiated cells are administered to the eye, where they integrate with existing structures to replace damaged or lost tissues.

Creation of pluripotent stem cells

Each one of us grew from a single cell with the capacity to generate every cell type present in our bodies. This inherent property, known as pluripotency, enables stem cells to develop a specific cellular identity in response to the activation of various regulatory genes.

Building on Nobel Prize–winning work, it is now possible for this differentiation process to be reversed, changing already-specialized cells back to their pluripotent state. The resulting cells, known as induced pluripotent stem cells (iPSCs), can then be re-differentiated into different cell types. Through this process, it is possible to create the highly specialized cells necessary for vision from iPSCs.

Differentiation into specialized ocular cells

There are a number of approaches to generate specialized ocular cells from pluripotent cells.

Neural cell types can be created by generating retinal organoids, which are three-dimensional structures containing primitive photoreceptors and other differentiated cells. Retinal organoids can be generated from iPSC when exposed to a particular combination of biochemical signals. Once matured, the photoreceptor precursor cells express light-sensitive pigments and transduce light into electrical signals. At the end of this maturation step, rod and cone photoreceptors are isolated and purified from the organoid to yield retinal photoreceptor progenitor cells. Additionally, retinal pigment epithelial cells can be created by exposing stem cells to specific chemical signals while they are attached to a specialized support matrix. This process creates islands of partially differentiated cells, which can then be selected and further expanded as fully differentiated cells.

Potential for genetic modification to improve function

In some applications there may be benefit from genetically modifying the pluripotent stem cells prior to differentiation, with the goal of improving performance of the cells, once they have been differentiated to the target cell type and transplanted. This may be achieved by deleting a gene (gene knock-out), adding a gene (gene knock-in), or through other modifications. We can perform any genetic modification at the stem cell stage, such that all subsequent differentiated cells will harbor this added genetically edited feature.

Transplantation into the eye

Advanced surgical techniques are available that enable the precise placement of new cells at the locations where they are needed.

In vivo

In nature, some animals such as fish and amphibians can regenerate specialized neuronal ocular cells after injury by reprogramming other structural cells in the eye. The latter first enter a progenitor like state that is further differentiated into selected cell types that replenish the lost structures. This approach has potential to regenerate a number of different neuronal ocular cell types.