Immunological Problems of Transplantation into the Subretinal Space

Abstract

The objective of retinal transplantation is to substitute destroyed or degenerated retina to improve visual function. Photoreceptors and retinal pigment epithelium cells of embryonic and nonembryonic origin have been transplanted into the subretinal space in different animal models. Recently, retinal cells have also been used for transplantation in untreated or immunosuppressed patients with retinitis pigmentosa and age-related macular degeneration. Transplants performed in animals such as the RCS rat have maintained retinal function at the transplantation site for long periods of time, although such transplantations in humans have not proved conclusively, to date, whether there is a real effect or not. One reason for this phenomenon seems to be an immune response to transplanted retinal cells at the transplantation site. The detectable rejection process shows that the posterior part of the eye is not absolutely immunologically privileged and that rejection is a serious problem in human retinal transplantation. Many questions concerning transplantation technique, graft treatment and postoperative treatment will be answered through more intensive experiments and clinical trials regarding the immunology. However, rejection of transplanted material is one of the main reasons why retinal transplantation has not yet proved successful.

Transplanted Olfactory Ensheathing Cells Reduce Retinal Degeneration in Royal College of Surgeons Rats

“…10,11 The ratio of OECs to ONFs mixture, as controlled by S100 and fibronectin staining in this study, was around 50/50. We have no evidence as to how long these allografts will be tolerated because the degree of immune privilege of the subretinal space is neither absolute nor permanent 35 ; However, the current demonstration of an acute protective effects of OECs/ONFs transplantation opens up new horizons in researches of RP therapeutic strategies. …”

Culture in vitro Modulation of Human Leukocyte Antigen Molecules and Costimulatory Molecules on Human Retinal Pigment Epithelium

“…The dendritic cells and macrophages take up the alloantigens from transplanted RPE, process them and subsequently present them to the host T cells, leading to the activation of T cells. Thus, long-term observation reveals that the allogeneic graft immunological rejection is a serious problem in RPE transplantation [2]. …”

“…The graft rejective reaction is one of the main reasons why retinal transplantation has not yet proved successful and must be solved before a clinical benefit can be reached [2, 3]. Many attempts have been made to culture RPE in vitro for the needs of research or the clinical application.…”

Stem cell therapies for retinal diseases: recapitulating development to replace degenerated cells

“…Although the subretinal space and the intravitreal cavity are relatively immune privileged sites, damage to the blood-retina barrier, leaky blood vessels and activated microglia cells that are present in diseased or injured eyes or induced by the surgery itself can cause immune rejection and inflammatory responses (Enzmann et al, 1998;Langmann, 2007). Indeed, immune rejection and inflammatory reactions have been observed after cell transplantation (Boyd et al, 2005).…”