Neurotrophic factors are important for the development and maintenance of the auditory system. They have also been shown to act as survival factors for auditory neurons in animal deafness models. Studies have demonstrated recently that these neurotrophic factors not only maintain survival of auditory neurons, but that these surviving neurons retain functionality. It remains to be determined, however, if a single administration of a neurotrophic factor is sufficient to maintain auditory neuron survival after loss of hair cells, or if sustained delivery is required. This study investigated the longevity of the survival effects of BDNF on auditory neurons in deafened guinea pigs. Briefly, the left cochleae of deafened guinea pigs were infused with BDNF for 28 days via a mini-osmotic pump, and neuronal survival was analyzed at various stages after the completion of treatment. BDNF treatment prevented the degeneration of auditory neurons that normally is seen after a loss of hair cells, supporting previous studies. Our results indicate, however, that cessation of BDNF treatment leads to an accelerated decline in auditory neuron survival as compared to that observed in deafened, untreated cochleae. These findings indicate that much work remains to be done to establish a technique for the long-term survival of auditory neurons in the deaf ear.

As key factors in the development and maintenance of the auditory system, neurotrophins can prevent auditory neuron degeneration when applied within three to five days of deafening. We tested each of the neurotrophins BDNF, NT-3, NT-4/5 and NGF for their ability to support auditory neuron survival following a two-week period of deafness in guinea pigs, when approximately 15% auditory neuron degeneration has already occurred. Although delayed, the treatment with each neurotrophin prevented further degeneration with similar efficacy.

Citation: Sinclair NC, Shivdasani MN, Perera T, et al.; for the Bionic Vision Australia Consortium. The appearance of phosphenes elicited using a suprachoroidal retinal prosthesis. Invest Ophthalmol Vis Sci. 2016;57:4948-4961. DOI:10.1167/ iovs.15-18991 PURPOSE. Phosphenes are the fundamental building blocks for presenting meaningful visual information to the visually impaired using a bionic eye device. The aim of this study was to characterize the size, shape, and location of phosphenes elicited using a suprachoroidal retinal prosthesis.METHODS. Three patients with profound vision loss due to retinitis pigmentosa were implanted with a suprachoroidal electrode array, which was used to deliver charge-balanced biphasic constant-current pulses at various rates, amplitudes, and durations to produce phosphenes. Tasks assessing phosphene appearance, location, overlap, and the patients' ability to recognize phosphenes were performed using a custom psychophysics setup.RESULTS. Phosphenes were reliably elicited in all three patients, with marked differences in the reported appearances between patients and between electrodes. Phosphene shapes ranged from simple blobs to complex forms with multiple components in both space and time. Phosphene locations within the visual field generally corresponded to the retinotopic position of the stimulating electrodes. Overlap between phosphenes elicited from adjacent electrodes was observed with one patient, which reduced with increasing electrode separation. In a randomized recognition task, two patients correctly identified the electrode being stimulated for 57.2% and 23% of trials, respectively.CONCLUSIONS. Phosphenes of varying complexity were successfully elicited in all three patients, indicating that the suprachoroidal space is an efficacious site for electrically stimulating the retina. The recognition scores obtained with two patients suggest that a suprachoroidal implant can elicit phosphenes containing unique information. This information may be useful when combining phosphenes into more complex and meaningful images that provide functional vision.

Sensorineural hearing loss, as a result of damage to or destruction of the sensory epithelia within the cochlea, is a common cause of deafness. The subsequent degeneration of the neural elements within the inner ear may impinge upon the efficacy of the cochlear implant. Experimental studies have demonstrated that neurotrophic factors can prevent this degeneration in animal models of deafness, and can even provide functional benefits. Neurotrophic factor therapy may, therefore, provide similar protective effects in humans, resulting in improved speech perception outcomes among cochlear implant patients. There are, however, numerous issues pertaining to delivery techniques and treatment regimes which need to be addressed prior to any clinical application. This review considers these issues in view of the potential therapeutic application of neurotrophic factors within the auditory system.