Retinal Cell Transplantation, Biomaterials, and In Vitro Models for Developing Next-generation Therapies of Age-related Macular Degeneration

Retinal pigment epithelium (RPE) cells grown on a scaffold, an RPE patch, have potential to ameliorate visual impairment in a limited number of retinal degenerative conditions. This tissue-replacement therapy is suited for age-related macular degeneration (AMD), and related diseases. RPE cells must be transplanted before the disease reaches a point of no return, represented by the loss of photoreceptors. Photoreceptors are specialized, terminally differentiated neurosensory cells that must interact with RPE’s apical processes to be functional. Human photoreceptors are not known to regenerate. On the RPE’s basal side, the RPE transplant must induce the reformation of the choriocapillaris, thereby re-establishing the outer blood-retinal barrier. Because the scaffold is positioned between the RPE and choriocapillaris, it should ideally degrade and be replaced by the natural extracellular matrix that separates these tissues. Besides biodegradable, the scaffolds need to be nontoxic, thin enough to not affect the focal length of the eye, strong enough to survive the transplant procedure, yet flexible enough to conform to the curvature of the retina. The challenge is patients with progressing AMD treasure their remaining vision and fear that a risky surgical procedure will further degrade their vision. Accordingly, clinical trials only treat eyes with severe impairment that have few photoreceptors to interact with the transplanted patch. Although safety has been demonstrated, the cell-replacement mechanism and efficacy remain difficult to validate. This review covers the structure of the retina, the pathology of AMD, the limitations of cell therapy approaches, and the recent progress in developing retinal therapies using biomaterials.