We provide strong support for the feasibility of an epiretinal neurotransmitter-based retinal prosthesis. Our findings suggest that chemical stimulation of RGCs is a viable alternative to electrical stimulation and could offer distinct advantages such as the selective stimulation of RGC somata.

Subretinal stimulation of the retina with neurotransmitters, the normal means of conveying visual information, is a potentially better alternative to electrical stimulation widely used in current retinal prostheses for treating blindness from photoreceptor degenerative diseases. Yet, no subretinal electrical or chemical stimulation study has stimulated the OFF and ON pathways differentially through inner retinal activation. Here, we demonstrate the feasibility of differentially stimulating retinal ganglion cells (RGCs) through the inner nuclear layer of the retina with glutamate, a primary neurotransmitter chemical, in a biomimetic way. We show that controlled pulsatile delivery of glutamate into the subsurface of explanted wild-type rat retinas elicits highly localized simultaneous inhibitory and excitatory spike rate responses in OFF and ON RGCs. We also present the spatiotemporal characteristics of RGC responses to subretinally injected glutamate and the therapeutic stimulation parameters. Our findings could pave the way for future development of a neurotransmitter-based subretinal prosthesis offering more naturalistic vision and better visual acuity than electrical prostheses.

Biomimetic stimulation of the retina with neurotransmitters, the natural agents of communication at chemical synapses, could be more effective than electrical stimulation for treating blindness from photoreceptor degenerative diseases. Recent studies have demonstrated the feasibility of neurotransmitter stimulation by injecting glutamate, a primary retinal neurotransmitter, into the retina at isolated single sites. Here, we demonstrate spatially patterned multisite stimulation of the retina with glutamate, offering the first experimental evidence for applicability of this strategy for translating visual patterns into afferent neural signals. To accomplish pattern stimulation, we fabricated a special microfluidic device comprising an array of independently addressable microports connected to tiny on-chip glutamate reservoirs via microchannels. The device prefilled with glutamate was interfaced with explanted rat retinas placed over a multielectrode array (MEA) with the retinal ganglion cells (RGC) contacting the electrodes and photoreceptor surface contacting the microports. By independently and simultaneously activating a subset of the microports with modulated pressure pulses, small boluses of glutamate were convectively injected at multiple sites in alphabet patterns over the photoreceptor surface. We found that the glutamate-driven RGC responses recorded through the MEA system were robust and spatially laid out in patterns strongly resembling the injection patterns. The stimulations were also highly localized with spatial resolutions comparable to or better than electrical retinal prostheses. Our findings suggest that surface stimulation of the retina with neurotransmitters in pixelated patterns of visual images is feasible and an artificial chemical synapse chip based on this approach could potentially circumvent the limitations of electrical retinal prostheses.

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Our objective was to carry out a prospective, randomized, single-blind study to evaluate whether light emitting diode (LED) phototherapy using a low-cost set of lights is as effective as conventional phototherapy in treating hyperbilirubinemia in neonates. The study included 45 pre-term neonates requiring phototherapy as per American Academy of Pediatrics guidelines; participants were randomized to receive phototherapy using LED-based lights, conventional fluorescent blue lights or conventional halogen lights. There were no statistically significant differences in the average bilirubin levels at the onset, at the maximum and at the end of treatment, nor in the duration of phototherapy treatment and the rate of decrease in bilirubin levels in the neonates receiving conventional fluorescent blue light, conventional halogen light and LED phototherapy. (Differences were considered significant at p < 0.05). The average rate of decrease of bilirubin levels was 0.047 ± 0.037 mg dl(-1) h(-1), 0.055 ± 0.056 mg dl(-1) h(-1) and 0.057 ± 0.045 mg dl(-1) h(-1) in the groups receiving conventional fluorescent blue light, conventional halogen light and LED phototherapy, respectively. The average duration of phototherapy treatment in the three groups was 108.8 ± 85.9 h, 92.8 ± 38.1 h, 110.4 ± 42.6 h, respectively. In this pilot study, LED phototherapy using a simple, low-cost set of lights was as effective as conventional phototherapy in the treatment of neonatal hyperbilirubinemia. LED phototherapy lights that deliver 30-40 µW cm(-2 )nm(-1) can be assembled in small quantities for