Retinal cell transplantation in retinitis pigmentosa

Abstract

Retinitis pigmentosa is the most common hereditary retinal disease. Dietary supplements, neuroprotective agents, cytokines, and lately, prosthetic devices, gene therapy, and optogenetics have been employed to slow down the retinal degeneration or improve light perception. Completing retinal circuitry by transplanting photoreceptors has always been an appealing idea in retinitis pigmentosa. Recent developments in stem cell technology, retinal imaging techniques, tissue engineering, and transplantation techniques have brought us closer to accomplish this goal. The eye is an ideal organ for cell transplantation due to a low number of cells required to restore vision, availability of safe surgical and imaging techniques to transplant and track the cells in vivo, and partial immune privilege provided by the subretinal space. Human embryonic stem cells, induced pluripotential stem cells, and especially retinal organoids provide an adequate number of cells at a desired developmental stage which may maximize integration of the graft to host retina. However, stem cells must be manufactured under strict good manufacturing practice protocols due to known tumorigenicity as well as possible genetic and epigenetic stabilities that may pose a danger to the recipient. Immune compatibility of stem cells still stands as a problem for their widespread use for retinitis pigmentosa. Transplantation of stem cells from different sources revealed that some of the transplanted cells may not integrate the host retina but slow down the retinal degeneration through paracrine mechanisms. Discovery of a similar paracrine mechanism has recently opened a new therapeutic path for reversing the cone dormancy and restoring the sight in retinitis pigmentosa.

Keywords: Photoreceptors; retina; retinitis pigmentosa; stem cells; transplantation.

Figure 1

Adult human photoreceptor sheet harvested with excimer laser. Inner retinal neurons were removed using excimer laser. A depth guidance method allows the operator to ablate tissues down to outer plexiform layer precisely. These grafts were subsequently used for the first human photoreceptor sheet transplantation

Figure 2

Transmission electron microphotograph after transplantation of adult photoreceptor sheet into rhesus monkey subretinal space. Host retinal pigment epithelial cells engulf outer segments of the (tOS) of the transplanted adult human photoreceptor cells. Patent choriocapillaris is seen below the retinal pigment epithelium