Investigation of Injection Depth for Subretinal Delivery of Exogenous Glutamate to Restore Vision via Biomimetic Chemical Neuromodulation

Chemical neuromodulation of the retina using native neurotransmitters to biomimetically activate target retinal neurons through chemical synapses is a promising biomimetic alternative to electrical stimulation for restoring vision in blindness caused by photoreceptor degenerative diseases. Recent research has shown that subretinal chemical stimulation could be advantageous for treating photoreceptor degenerative diseases but many of the parameters for achieving efficacious chemical neuromodulation are yet to be explored. In this paper, we investigated how the depth at which neurotransmitter is injected subretinally affects the success rate, spike rate characteristics (i.e., amplitude, response latency, and time width), and spatial resolution of chemical stimulation in wild-type Long Evans and photoreceptor degenerated S334ter-3 transgenic rat retinas in vitro. We compared the responses to injections of glutamate at the subretinal surface and two subsurface depths near the outer and inner plexiform layers and found that while injections at all depths elicited robust retinal ganglion cell responses, they differed significantly in terms of the spike rate characteristics and spatial resolutions across injection depths. Shallow subsurface injections near the outer plexiform layer evoked the highest spike rate amplitudes and had the highest spatial resolution and success rates, while deep subsurface injections near the inner plexiform layer elicited the shortest latencies and narro...
Source: IEEE Transactions on Biomedical Engineering - Category: Biomedical Engineering Source Type: research

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Source: Journal of Immunoassay and Immunochemistry - Category: Biochemistry Tags: J Immunoassay Immunochem Source Type: research
Glaucoma is a globally unmet medical challenge and the most prevalent neurodegenerative disease, which permanently damages the optic nerve and retinal ganglion cells (RGCs), leading to irreversible blindness. Present therapies target solely at lowering intraocular ocular pressure (IOP), a major risk factor of the disease; however, elevated IOP is neither necessary nor sufficient to cause glaucoma. Glaucomatous RGC and nerve fiber loss also occur in individuals with normal IOP. Recent studies have provided evidence indicating a link between elevated IOP and T cell-mediated autoimmune responses, particularly that are specifi...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
Authors: Reinehr S, Grotegut P, Tsai T, Wagner N, Joachim SC Abstract In view of the aging members of our society, there will be an increase in severe visual impairment and blindness, also due to glaucoma, in the coming years. Therapy options are limited to treat occurring symptoms. Currently, only a deceleration of the pathogenesis progression, but no cure, is available. Therefore, it is necessary to develop new therapeutic strategies to treat glaucoma adequately and effectively, thus improving the quality of life of those affected. One possible approach seems to be primary neuroprotection, which acts independentl...
Source: Klinische Monatsblatter fur Augenheilkunde - Category: Opthalmology Tags: Klin Monbl Augenheilkd Source Type: research
This study investigated the effect of PTEN/SOCS3 genetic deletion on the structural integrity of RGC dendrites and axons in the retina following optic nerve crush. Using time lapse, in vivo confocal scanning laser ophthalmoscopy to serially image dendritic and axonal arborizations of RGCs over six months after injury, RGC dendrites and axons were only preserved in Thy-1-YFP/PTEN-/- and Thy-1-YFP/PTEN-/-SOCS3-/- mice, and axons in the retina regenerated at a rate of 21.1  μm/day and 15.5  μm/day, respectively. By contrast, dendritic complexity significantly decreased in Thy-1-YFP-SOCS3-/- and control mice at a...
Source: Experimental Eye Research - Category: Opthalmology Authors: Tags: Exp Eye Res Source Type: research
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Source: Current Opinion in Neurology - Category: Neurology Tags: NEURO-OPHTHALMOLOGY: Edited by Heather E. Moss Source Type: research
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Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
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Source: Experimental Eye Research - Category: Opthalmology Authors: Tags: Exp Eye Res Source Type: research
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Source: Restorative Neurology and Neuroscience - Category: Neurology Tags: Restor Neurol Neurosci Source Type: research
AbstractGlaucoma is the second leading cause of blindness worldwide. Even though significant advances have been made in its management, currently available antiglaucoma therapies suffer from considerable drawbacks. Typically, the success and efficacy of glaucoma medications are undermined by their limited bioavailability to target tissues and the inadequate adherence demonstrated by patients with glaucoma. The latter is due to a gradual decrease in tolerability of lifelong topical therapies and the significant burden to patients of prescribed stepwise antiglaucoma regimens with frequent dosing which impact quality of life....
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