Dataset Information

A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy.

ABSTRACT: PURPOSE:Stem and progenitor cell transplantation provides a promising clinical application for treating degenerative retinal diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Our previous studies have shown that a single subretinal injection of human cortical-derived neural progenitor cells (hNPCctx) into cyclosporine-treated Royal College of Surgeons (RCS) rats preserved both photoreceptors and visual function. However, it is still unknown whether nonautologous progenitor cell readministration for sustained vision is efficacious and safe in terms of the initial graft initiating an immune response to a subsequent graft. METHODS:A cell suspension containing 3×104 hNPCctx into one eye of cyclosporine-treated RCS rats at postnatal day 21 (P21), followed by a second transplantation at P95 into the previously untreated fellow eye. RESULTS:hNPCctx delayed photoreceptor degeneration and preserved visual function, as measured by electroretinography (ERG), optokinetic response (OKR), and luminance threshold recordings (LTRs). Visual function and photoreceptors of the initially treated eye were still preserved 6 weeks after hNPCctx were injected into the second eye. Antibodies against T-cell markers showed that CD3, CD4, and CD8 T cells were not detected at P90 and P140 in most cases. No detectable level of anti-nestin antibody was found in serum by enzyme-linked immunosorbent assay (ELISA). CONCLUSIONS:This xenograft study with cyclosporine-treated animals demonstrates that readministration of hNPCctx into the fellow eye did not induce anti-graft immune responses or lower therapeutic efficacy of hNPCctx in preserving vision. Thus, readministration of progenitor cells to sustain long-term efficacy may be an option for long-term therapies of retinal degeneration. TRANSLATIONAL RELEVANCE:Redosing neural progenitors do not affect the efficacy of the initial grafts in protecting vision or induce unwanted immune responses.

SUBMITTER: Lu B

PROVIDER: S-EPMC4324446 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy.

Lu Bin B Lin Yanhua Y Tsai Yuchun Y Girman Sergey S Adamus Grazyna G Jones Melissa K MK Shelley Brandon B Svendsen Clive N CN Wang Shaomei S

Translational vision science & technology 20150210 1

<h4>Purpose</h4>Stem and progenitor cell transplantation provides a promising clinical application for treating degenerative retinal diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Our previous studies have shown that a single subretinal injection of human cortical-derived neural progenitor cells (hNPC<sup>ctx</sup>) into cyclosporine-treated Royal College of Surgeons (RCS) rats preserved both photoreceptors and visual function. However, it is still unkn ...[more]

PMID: 25694843

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Project description:Retinal prostheses have shown some clinical success in patients with retinitis pigmentosa and age-related macular degeneration. However, even after the implantation of a retinal prosthesis, the patient's visual acuity is at best less than 20/420. Reduced visual acuity may be explained by a decrease in the signal-to-noise ratio due to the spontaneous hyperactivity of retinal ganglion cells (RGCs) found in degenerate retinas. Unfortunately, abnormal retinal rewiring, commonly observed in degenerate retinas, has rarely been considered for the development of retinal prostheses. The purpose of this study was to investigate the aberrant retinal network response to electrical stimulation in terms of the spatial distribution of the electrically evoked RGC population. An 8 × 8 multielectrode array was used to measure the spiking activity of the RGC population. RGC spikes were recorded in wild-type [C57BL/6J; P56 (postnatal day 56)], rd1 (P56), rd10 (P14 and P56) mice, and macaque [wild-type and drug-induced retinal degeneration (RD) model] retinas. First, we performed a spike correlation analysis between RGCs to determine RGC connectivity. No correlation was observed between RGCs in the control group, including wild-type mice, rd10 P14 mice, and wild-type macaque retinas. In contrast, for the RD group, including rd1, rd10 P56, and RD macaque retinas, RGCs, up to approximately 400-600 μm apart, were significantly correlated. Moreover, to investigate the RGC population response to electrical stimulation, the number of electrically evoked RGC spikes was measured as a function of the distance between the stimulation and recording electrodes. With an increase in the interelectrode distance, the number of electrically evoked RGC spikes decreased exponentially in the control group. In contrast, electrically evoked RGC spikes were observed throughout the retina in the RD group, regardless of the inter-electrode distance. Taken together, in the degenerate retina, a more strongly coupled retinal network resulted in the widespread distribution of electrically evoked RGC spikes. This finding could explain the low-resolution vision in prosthesis-implanted patients.

Dataset Information

A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy.

Publications

A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy.

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