Transplanted neurons integrate into adult retinas and respond to light

Venugopalan, Praseeda; Wang, Yan; Nguyen, Tu; Huang, Abigail E.; Muller, Kenneth J.; Goldberg, Jeffrey L.

doi:10.1038/ncomms10472

Cited by 142 publications

(150 citation statements)

References 46 publications

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“…Emerging therapeutic interventions intended to restore vision in glaucoma patients, such as RGC transplantation [178] and artificial retinal implants [120], will need to consider the condition of the posterior visual pathway as a confounding factor in the efficacy of therapeutic interventions, including the extent of regeneration of the brain’s visual centres in response to reanimation of the anterior visual pathway [141]. The observation of glaucomatous neurodegeneration in the brain also has implications for assessing the efficacy of neuroprotective therapies, suggesting that the focus of these therapies should be extended to include the whole CNS and that the visual centres of the brain should be included as endpoints in studies of therapeutic efficacy in glaucoma trials [141].…”

Section: Techniques For Monitoring Retinal Ganglion Cell Healthmentioning

confidence: 99%

Glaucoma: the retina and beyond

Davis¹,

Crawley

Pahlitzsch³

et al. 2016

Acta Neuropathol

228

151

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Over 60 million people worldwide are diagnosed with glaucomatous optic neuropathy, which is estimated to be responsible for 8.4 million cases of irreversible blindness globally. Glaucoma is associated with characteristic damage to the optic nerve and patterns of visual field loss which principally involves the loss of retinal ganglion cells (RGCs). At present, intraocular pressure (IOP) presents the only modifiable risk factor for glaucoma, although RGC and vision loss can continue in patients despite well-controlled IOP. This, coupled with the present inability to diagnose glaucoma until relatively late in the disease process, has led to intense investigations towards the development of novel techniques for the early diagnosis of disease. This review outlines our current understanding of the potential mechanisms underlying RGC and axonal loss in glaucoma. Similarities between glaucoma and other neurodegenerative diseases of the central nervous system are drawn before an overview of recent developments in techniques for monitoring RGC health is provided, including recent progress towards the development of RGC specific contrast agents. The review concludes by discussing techniques to assess glaucomatous changes in the brain using MRI and the clinical relevance of glaucomatous-associated changes in the visual centres of the brain.

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Section: Techniques For Monitoring Retinal Ganglion Cell Healthmentioning

confidence: 99%

Glaucoma: the retina and beyond

Davis¹,

Crawley

Pahlitzsch³

et al. 2016

Acta Neuropathol

228

151

View full text Add to dashboard Cite

show abstract

“…14 Photoreceptor generation from hESCs has progressed more rapidly than has generation of RGCs. 94,95 Whilst hESC technology is in essence still embryonic, with ethical and scientific challenges, it has the potential to revolutionalize the management of ocular neurodegenerative disease considered incurable through neuroregeneration of functioning retinal neurons. 49 Preclinical studies (in mature uninjured rat and monkey eyes) have previously demonstrated the ability of retinal cells derived from hESCs to survive, integrate into the host retina and mediate light responses.…”

Section: Human Embryonic Stem Cellsmentioning

confidence: 99%

Neuroprotection in glaucoma: recent advances and clinical translation

Guymer

Wood

Chidlow

et al. 2018

Clinical Exper Ophthalmology

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Intraocular pressure (IOP) reduction is currently the only evidence-based treatment strategy for glaucoma. However, IOP control in some individuals is challenging. Despite optimal treatment, a significant proportion of individuals will progress, with loss of visual field, loss of driving vision and impaired quality of life. A new modality that could augment current treatment and reduce the rate of neurodegeneration to preserve vision throughout life would be a major breakthrough. A vast number of studies have reported effective neuroprotection in animal models of glaucoma; however, translation to the clinic remains a major hurdle. Herein, we explore the therapeutic advancements in non-IOP-dependent neuroprotection research based upon potential pathogenic mechanisms and propose strategies to improve the clinical translation of neuroprotective research in glaucoma.

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“…Successful transplantation of RGCs has been reported (MacLaren et al, 2006;Venugopalan et al, 2016). RGCs receive visual information from photoreceptors via two intermediate neurons: bipolar and amacrine cells.…”

Section: Takahisa Suzuki | Keita Oochi | Satoko Hakeda-suzuki | Takasmentioning

confidence: 99%

Transplantation of photoreceptor precursor cells into the retina of an adult Drosophila

et al. 2018

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Blindness caused by the disconnection between photoreceptor cells and the brain can be cured by restoring this connection through the transplantation of retinal precursor neurons. However, even after transplanting these cells, it is still unclear how to guide the axons over the long distance from the retina to the brain. To establish a method of guiding the axons of transplanted neurons, we used the Drosophila visual system. By testing different conditions, including the dissociation and preincubation length, we have successfully established a method to transplant photoreceptor precursor cells isolated from the developing eye discs of third-instar larvae into the adult retina. Moreover, we overexpressed N-cadherin (CadN) in the transplant, since it is known to be broadly expressed in the optic lobe well after developmental stages, continuing through adult stages. We found that promoting the cell adhesive properties using CadN enhances the axonal length of the grafted photoreceptor neurons and therefore is useful for future transplantation. We tested the overexpression of a CadN::Frazzled chimeric receptor and found that there was no difference in axonal length from our wild-type transplants, suggesting that the intracellular domain of CadN is necessary for axonal elongation. Altogether, using the Drosophila visual system, we have established an excellent platform for exploring the molecules required for proper axon extension of transplanted neuronal cells. Future studies building from this platform will be useful for regenerative therapy of the human nervous system based on transplantation.

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Transplanted neurons integrate into adult retinas and respond to light

Cited by 142 publications

References 46 publications

Glaucoma: the retina and beyond

Glaucoma: the retina and beyond

Neuroprotection in glaucoma: recent advances and clinical translation

Transplantation of photoreceptor precursor cells into the retina of an adult Drosophila

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