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    New approaches and technologies offer hope in vision restoration



    “Some of these regenerating axons are homing in on the appropriate brain nuclei,” said Larry Benowitz, PhD, director, Laboratories for Neuroscience Research in Neurosurgery, Boston Children’s Hospital, and professor of neurosurgery and ophthalmology, Harvard Medical School, Boston. “They are probably forming synapses. The bad news is that at last two-thirds of RGCs die after optic nerve injury in animal models and only about 10% of the remaining RGCs regenerate axons.”

    In searching for a way to increase RGC regeneration, researchers focused on zinc. Zinc accumulates in retinal synapses after optic nerve injury, then migrates to RGCs. Removing zinc by chelation promotes both RGC survival and axon regeneration.

    Related: Collaboration needs to exist between retinal, glaucoma specialists

    “If we combine zinc chelation with pten deletion, we can get some axons to regenerate the entire length of the optic nerve,” Dr. Benowitz reported. “While we have not yet studied this activity extensively in glaucoma, we can get about half of the RGCs surviving for months after injury.”


    Stem cell therapy

    The National Eye Institute (NEI) has a simple goal: to regenerate neurons and neural connections in the eye and visual system. Research teams are focusing on photoreceptor loss, ganglion cell injury, and optic nerve regeneration using induced pluripotent stem cells (iPS).

    Recent: The lens regrowth hypothesis

    “For all practical purposes, iPS are the equivalent of embryonic stem cells, but we can make them from any adult,” said Kapil Bharti, PhD, Stadtman Investigator at the NEI’s Unit of Ocular Stem Cell & Translational Research. “We can take 20 mL of your blood and reprogram it to become iPS, hence no political issues. The other advantage is that these cells are personalized. We can make cell therapy for one single patient.”

    NEI researchers are developing a three-dimensional model of the back of the eye for in vitro-disease modeling, drug testing, and cell therapy to restore vision. The initial project is focused on age-related macular degeneration (AMD), Dr. Bharti said, but the same platform should be translatable to glaucoma and other visual diseases.

    More: Exploring lens regeneration after cataract surgery

    In AMD, retinal pigment epithelial (RPE) cell atrophy leads to the death of photoreceptor cells and impaired vision. Using bioprinting and tissue-engineering techniques, the team has created an iPS-derived RPE patch. The system has been scaled up to a five-month, GMP-manufacturing process capable of producing clinical product, an implantable RPE patch that can be implanted. Human RPE patches have been successfully implanted in pigs to treat laser-induced RPE ablation.

    Detection: Ceeable aims to be the next gold standard in visual fields

    “We hope to start a clinical trial in 2018 using autologous patches in AMD,” Dr. Bharti said. “This same manufacturing process will leverage many more clinical investigation in other iPS cell types.”


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