Background. A visual prosthesis is a conceptual device designed to activate residual functional neurons in the visual pathway of blind individuals to produce artificial vision. Such device, when applied to stimulate the vitreous surface of the retina, has proven feasible in producing patterned light perception in blind individuals suffering from dystrophic diseases of the retina, such as aged-related macular degeneration (AMD). However the practicality of such approach has been challenged by the difficulty of surgical access and the risks of damaging the neuroretina. Positioning a visual implant over the scleral surface of the eye could present a safer alternative but this stimulation modality has not been tested in diseased retinas. Additionally, recent research has shown that the adult neocortex retains substantial plasticity following a disruption to its visual input and the potential deterioration in visual capabilities as a result of such experience modification may undermine the overall bionic rescue strategy. Methods. Two animal models mimicking the principal pathologies found in AMD, namely photoreceptor degeneration and reduced retinal ganglion cell mass, were used to evaluate the efficacy of trans-scleral stimulation of the retina by recording electrical evoked potentials in the visual cortex. The visual performance following the loss of pattern vision induced by bilateral eyelid suturing in adult mice was examined by analysing visual evoked potentials. Findings. Spatially differentiated cortical activations were obtained notwithstanding the underlying retinopathy in the experiment animals. The charge density thresholds were found to be similar to controls and below the bioelectric safety limit. After prolonged visual deprivation (weeks) in the mouse, the visual cortical responses evoked by either electrical or photic stimuli were both significantly reduced. An assessment of different visual capabilities using patterned stimuli demonstrated that whilst visual acuity and motion sensitivity were preserved, significant depression in luminance and contrast sensitivities was detected. Conclusion. Trans-scleral stimulation of the retina is a feasible approach for the development of a visual prosthesis. Following visual loss the adult brain exhibits significant experience-dependent modifications. These new insights may force a revision on the current bionic rescue strategy.

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