Utilizing Stem Cell-Derived RPE Cells as A Therapeutic Intervention for Age-Related Macular Degeneration

Abstract

Degeneration or dysfunction of the retinal pigment epithelium (RPE) can induce secondary photoreceptor atrophy and catastrophic vision loss in patients with age-related macular degeneration (AMD). AMD is the leading cause of vision loss in the elderly in industrialized countries and no cure exists for the "dry" or atrophic form to date. However, recent pre-clinical data from several groups suggests that embryonic stem cell-derived RPE cell transplantation may prevent photoreceptor degeneration in animal models of RPE degeneration. Another approach may be to derive RPE cells from autologous induced pluripotent stem cells (iPSCs) reprogrammed from dermal tissue. However, the safety of this approach has been questioned on several levels. In this chapter we will summarize work reported by several groups, including our own, that clearly demonstrate that transplanted RPE cells can provide anatomical and functional photoreceptor rescue in animal models of retinal degeneration. We will also discuss some of the prevailing concerns and challenges associated with this technique.

Cellular models and therapies for age-related macular degeneration

“…Future models and therapies might also take advantage of layered retinal tissues that spontaneously form in stem-cell cultures ( Westenskow et al, 2014 ). A structure similar to the embryonic optic cup, which contains integrated RPE and neurosensory layers, can self-organize in mouse and human stem-cell cultures ( Zhong et al, 2014 ; Eiraku and Sasai, 2012 ).…”

Retinal pigment epithelium expansion around the neural retina occurs in two separate phases with distinct mechanisms

“…While much is known about RPE function in the adult retina, little is known about the early development of the RPE and how the epithelium comes to wrap around the back of the neural retina. Such knowledge could benefit RPE cell transplant and stem cell therapies for the treatment of retinal degenerative disorders (Carr et al, ; Westenskow et al, ).…”

A novel AhR ligand, 2AI, protects the retina from environmental stress

“…Dysregulation of this function has a potential to play a role in the degeneration of the retina 5 . Overall, it has been ascertained that the functional disruption and atrophy of the RPE is a key factor in the progression of degenerative conditions in the retina, leading to the death of other cell types in the retina, including the rod and cone photoreceptors, resulting in significant vision loss 6 7 . Therefore, developing strategies to maintain the function and cellular homeostasis of the RPE is a significant point of investigation with regards to preventing retinal degeneration in humans.…”