Retinal transplantation: progress and problems in clinical application

Abstract

There is currently no real treatment for blinding disorders that stem from the degeneration of cells in the retina and affect at least 50 million individuals worldwide. The excitement that accompanied the first studies showing the potential of retinal cell transplantation to alleviate the progress of blindness in such diseases as retinitis pigmentosa and age-related macular degeneration has lost some of its momentum, as attempts to apply research to the clinic have failed so far to provide effective treatments. What these studies have shown, however, is not that the approach is flawed but rather that the steps that need to be taken to achieve a viable, clinical treatment are many. This review summarizes the course of retinal transplant studies and points to obstacles that still need to be overcome to improve graft survival and efficacy and to develop a protocol that is effective in a clinical setting. Emphasis is given particularly to the consequences of introducing transplants to sites that have been considered immunologically privileged and to the role of the major histocompatibility complex classes I and II molecules in graft survival and rejection.

Retinal transplants evaluated by optical coherence tomography in photoreceptor degenerate rats

“…Retinal transplantation has been studied as a potential therapeutic strategy for preservation of vision in retinal degenerative diseases (Lund et al, 2003;Aramant and Seiler, 2004). In rats, intact sheets of fetal retina can be transplanted into the subretinal space of retinal degenerate rats to restore the damaged retina (Seiler and Aramant, 1998).…”

Inherited retinal degenerations: therapeutic prospects

“…Transplantation of either embryonic dissociated cells or retinal sheets into the subretinal space of rodent models of retinal degeneration demonstrate that transplants survive and differentiate and that neuronal fibers originating from the transplant develop synapses with the remaining host retina which are at least sufficient to mediate a simple light-dark preference (Kwan et al, 1999;Aramant and Seiler, 1995). Still, numerous obstacles remain before RPE or retinal transplantations may be used in clinical therapy (see reviews by Berson and Jakobiec, 1999;Lund et al, 2003).…”

“…gene therapy (see Farrar et al, 2002 andDejneka et al, 2003)], slowing down or even stopping the process of photoreceptor degeneration [growth factors or calcium blockers applications (see Chaum, 2003;Frasson et al, 1999b), vitamin A supplementation (Berson et al, 1993a(Berson et al, ,1993b], preserving the cones implicated in the central visual function [identification of endogenous cone viability factors (Léveil-lard et al, 2004)] or even replacing the lost cells [transplantation (see Lund et al, 2003), use of stem or precursor cells (see Ahmad, 2001)]. Still, many obstacles will need to be overcome before most of these strategies can be applied to humans.…”

Combined Therapies in the Treatment of Neurotrauma: Polymers, Bridges and Gene Therapy in Visual System Repair

“…Effective and consistent replacement of lost neurons in the retina using transplantation methods has proved difficult [8] ; a more productive therapeutic approach may be, if circumstances permit, to intervene earlier in the degenerative process. Early diagnosis of degenerative/ chronic diseases, or the earliest possible intervention after trauma, would allow the use of therapies that may prevent or substantially slow further deterioration of compromised endogenous cells.…”