Surgical Approaches for Cell Therapeutics Delivery to the Retinal Pigment Epithelium and Retina

Adv Exp Med Biol. 2019:1186:141-170. doi: 10.1007/978-3-030-28471-8_6.

Abstract

Developing successful surgical strategies to deliver cell therapeutics to the back of the eye is an essential pillar to success for stem cell-based applications in blinding retinal diseases. Within this chapter, we have attempted to gather all key considerations during preclinical animal trials.Guidance is provided for choices on animal models, options for immunosuppression, as well as anesthesia. Subsequently we cover surgical strategies for RPE graft delivery, both as suspension as well as in monolayers in small rodents, rabbits, pigs, and nonhuman primate. A detailed account is given in particular on animal variations in vitrectomy and subretinal surgery, which requires a considerable learning curve, when transiting from human to animal. In turn, however, many essential subretinal implantation techniques in large-eyed animals are directly transferrable to human clinical trial protocols.A dedicated subchapter on photoreceptor replacement provides insights on preparation of suspension as well as sheet grafts, to subsequently outline the basics of subretinal delivery via both the transscleral and transvitreal route. In closing, a future outlook on vision restoration through retinal cell-based therapeutics is presented.

Keywords: Age-related macular degeneration; Anesthesia; Cell replacement; Cell-based therapy; Immunosuppression; Monkey; Mouse; Nonhuman primate; Photoreceptor; Pig; Preclinical study; Rabbit; Rat; Retinal pigment epithelium; Surgery; Transplantation; Vitrectomy.

MeSH terms

  • Animals
  • Cell- and Tissue-Based Therapy*
  • Humans
  • Immunosuppression Therapy
  • Models, Animal
  • Photoreceptor Cells / cytology
  • Retina* / surgery
  • Retinal Diseases* / surgery
  • Retinal Diseases* / therapy
  • Retinal Pigment Epithelium* / surgery