Retinal repair by transplantation of photoreceptor precursors

  title={Retinal repair by transplantation of photoreceptor precursors},
  author={Robert E. MacLaren and Rachael A. Pearson and A. MacNeil and Ronald H. Douglas and Thomas E. Salt and Masayuki Akimoto and Anand Swaroop and Jane C. Sowden and Robin R Ali},
Photoreceptor loss causes irreversible blindness in many retinal diseases. Repair of such damage by cell transplantation is one of the most feasible types of central nervous system repair; photoreceptor degeneration initially leaves the inner retinal circuitry intact and new photoreceptors need only make single, short synaptic connections to contribute to the retinotopic map. So far, brain- and retina-derived stem cells transplanted into adult retina have shown little evidence of being able to… 

Restoration of vision after transplantation of photoreceptors

Evidence of functional rod-mediated vision after photoreceptor transplantation in adult Gnat1−/− mice is provided and it is demonstrated that visual signals generated by transplanted rods are projected to higher visual areas, including V1.

Reversal of end-stage retinal degeneration and restoration of visual function by photoreceptor transplantation

It is shown that transplanted rod precursors can reform an anatomically distinct and appropriately polarized outer nuclear layer of photoreceptor cells, and visual function was restored in animals with zero rod function at baseline, suggesting that a cell therapy approach may reconstitute a light-sensitive cell layer de novo and repair a structurally damaged visual circuit.

Transplanted photoreceptor precursors transfer proteins to host photoreceptors by a mechanism of cytoplasmic fusion

It is shown that host cells are labelled with the donor marker through cytoplasmic transfer, and the occurrence of Cre-Lox recombination between donor and host photoreceptors is detected, which may provide alternate therapeutic strategies at earlier stages of retinal degeneration.

Migration, integration and maturation of photoreceptor precursors following transplantation in the mouse retina.

A comprehensive histological analysis of the 6-week period following rod transplantation in mice showed the restoration of visual function mediated by transplanted photoreceptors correlated with the later expression of rod α-transducin, achieving maximal function by 5 weeks.

The Retinal Pigment Epithelium: a Convenient Source of New Photoreceptor cells?

Recent success in restoring visual function through photoreceptor replacement in mouse models of photoreceptor degeneration intensifies the need to generate or regenerate photoreceptor cells for the

Progenitor Cell Transplantation for Retinal Disease

Research areas of ongoing interest include detailed examination of marker expression, alternate potential cell types, optimization of proliferation and differentiation, genetic modification of donor cells, elucidation of the role of stem cells in cancer, assuring cessation of proliferation following transplantation, and the use of biodegradable materials as a substrate for cell delivery.

Subretinal transplantation of MACS purified photoreceptor precursor cells into the adult mouse retina.

Injection of enriched cell suspensions into the subretinal space of adult wild-type mice resulted in a 3-fold higher integration rate compared to unsorted cell suspensions, and magnetic-associated cell sorting (MACS) - enrichment of transplantable rod photoreceptor precursors isolated from the neonatal retina of Photoreceptor-specific reporter mice based on the cell surface marker CD73 is shown.



Survival and differentiation of cultured retinal progenitors transplanted in the subretinal space of the rat.

The survival and differentiation of cultured retinal progenitor grafts upon subretinal transplantation are reported and suggest that cultured retina progenitors can be a viable reagents for therapeutic transplantation.

Retinopathy induced in mice by targeted disruption of the rhodopsin gene

These animals should provide a useful genetic background on which to express other mutant opsin transgenes, as well as a model to assess the therapeutic potential of re-introducing functional rhodopsin genes into degenerating retinal tissues.

Incorporation of murine brain progenitor cells into the developing mammalian retina.

The age of the host appeared to play a key role in determining cell fate in vivo, and mBPCs survived and morphologically integrated after xenotransplantation without immunosuppression.

Transplantation of Neural Progenitor Cells into the Developing Retina of the Brazilian Opossum: An in vivo System for Studying Stem/Progenitor Cell Plasticity

The results suggest that the age of the host environment can strongly influence NPC differentiation and integration within the developing retina of the Brazilian opossum.

Differential effect of the rd mutation on rods and cones in the mouse retina.

A central to peripheral temporal gradient of degeneration exists, such that some rod nuclei persist in the far periphery up to day 47, but none is found at day 65.

Targeting of GFP to newborn rods by Nrl promoter and temporal expression profiling of flow-sorted photoreceptors.

The Maf-family transcription factor Nrl is a key regulator of photoreceptor differentiation in mammals and it is shown that a 2.5-kb Nrl promoter segment directs the expression of enhanced GFP specifically to rod photoreceptors and the pineal gland of transgenic mice.

Differential lineage restriction of rat retinal progenitor cells in vitro and in vivo

The data suggest that the adult retina retains epigenetic signals that are either restrictive for neuronal differentiation or instructive for glial differentiation, and induction of lineage‐specific cell differentiation of engrafted NRPCs to facilitate retinal repair will likely require initiation of specific differentiation in vitro prior to grafting and or modification of the host environment concomitantly with NRPC grafting.

Rods and cones in the mouse retina. II. Autoradiographic analysis of cell generation using tritiated thymidine

The findings demonstrate that rods and cones are developmentally distinct cell types in the mouse retina.

Nrl is required for rod photoreceptor development

It is reported that deletion of Nrl in mice results in the complete loss of rod function and super-normal cone function, mediated by S cones, and postulate that Nrl acts as a 'molecular switch' during rod-cell development by directly modulating rod-specific genes while simultaneously inhibiting the S-cone pathway through the activation of Nr2e3.