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SwitchBoard is an In Innovative Training Network (ITN) funded by the European Commission's Horizon 2020 programme under the Marie Curie Actions. The duration of the project is 48 months, starting on November 01, 2015.

The switchBoard consortium brings together eleven beneficiaries from eight different countries, combining the expertise of seven academic partners with excellent research and teaching records, one non-profit research organisation, and three fully integrated private sector partners. This European Training Network (ETN) is supported by six Partner Organisations as well as a management team experienced in multi-site training activities and counselled by a scientifically accomplished advisory board.

Taken together, the switchBoard training network provides an international, interdisciplinary platform to educate young scientists at the interface of neurobiology, information processing and neurotechnology.

Tuesday, 13 June 2017

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RETINAL PROSTHESIS

A REVIEW BY MENG-JUNG LEE

The main purpose of science is to help people obtain a better understanding of the world and to give us a better future. Researches in neurological field make us not only get a closer look to the delicacy of neurons, more importantly, help human kind to solve neuronal diseases. Scientists have been working on developing prostheses to improve the quality of lives from patients suffering from neurodegenerative diseases. The development of retinal implants, like other prostheses, aim to restore vision for the blind. Here I briefly introduce the principles of retinal prostheses and summarize some representative projects.

Concepts of Retinal Implants

Retinae are composed by very well organized layers of neurons, the photoreceptor layer, the inner nuclear layer and ganglion cell layer (check our other article ‘RETINA: OUR RULES AND CELLS WHO VIOLATE THEM’ for more detail). Most of the retinal implants are designed to benefit patients from retinitis pigmentosa (RP) or age-related macular degeneration (AMD), whose photoreceptor layers degenerate  eventually causing irreversible vision loss. However, most of the patients, even after years of suffering from these diseases, still have the remaining inner cells and ganglion cells in well contact (Weiland et al., 2011). To recover the vision, all we need is to find a good way to compensate the loss of photoreceptors; that is, a device that can sense  light and send the vision signals to the remaining retinal neurons. Therefore, the main task of retinal prostheses is to transform the light signals into electrical signals that retinae can understand.  



Retinal implants are most commonly implemented in three approaches: subretinal, epiretinal and suprachoroidal (Zrenner, 2013).

In the subretinal approach, the implant is placed right between the pigment epithelial layer, which is the layer right next to photoreceptor layer, and the (lost) photoreceptor layer. This kind of implants are usually made by light-sensitive photodiodes that make them able to transfer the light into small currents. They play the role of photoreceptors and rely on the remaining neuronal network for the rest of signal transduction. The advantages of implants from subretinal side are therefore 1. Easy positioning 2. Directly replace the damaged photoreceptors 3. No external cameras are required. 

However, they currently  face the problem of power supply, meaning they either need  huge amount of light in order to generate sufficient current, usually a lot higher than the light from nature environment. Patients today  need to carry an external power source which provides sufficient voltage for stimulation.
On the other hand, epiretinal implants are placed directly on the retinal ganglion cell layer. As retinal ganglion cells act as the output of the visual signal to the brain, implants no longer rely on the remaining neural network; instead, the implant itself directly transfers the images into electrical pulses to the optic nerve. For that reason, epiretinal implants are accompanied by external cameras. The electrical stimuli, compared to subretinal approach, act  directly onto the ganglion cells or their axons and could also help patients even there are barely no remaining healthy cells. Disadvantages are that they are harder to fix on retina since only one side of the implant is attached to the retina, they need an extra force to stabilize the position. More importantly, this approach will need the full understanding of the activities from dozens types of retinal ganglion cells without activating axons of passage.  
In the suprachoroidal approach  the implant is placed between choroid and sclera, and is similar to subretinal approach; however stimulating from a larger distance and therefore requiring larger electrodes. (Luo and da Cruz, 2014).

Few Representative Examples
Argus® II

The Argus® II prosthesis implement a 60 electrodes micro electrode arrays (MEAs) in an epiretinal fashion. Images are captured by a video processing unit adapted to eyeglasses, later on sent to the implant in a wireless way. This implant  has  received a CE mark for medical devices (for Europe) and FDA approval :Currently  more than 100 patients have received these implants.
This implant help patients with bare or no light perception to increase their abilities of recognize and discriminate forms, localize targets, detect motion, and navigate. The best visual acuity is reported by 20/1262.
Alpha-IMS
Each of the Alpha-IMS implants comprises  1500 photosensitive pixels and is implanted in the subretinal side of the fovea, the area with the highest visual acuity. The photodiodes capture light and transfer it into stimulation currents, which activate downstream inner neurons; The external power supply is magnetically attached to a subdermal internal coil (Stingl et al., 2013). This implant has also been commercially available in Europe and is going through human clinical trial. Patients with Alpha IMS implants restore partially the ability of recognition of objects and help them avoid dangerous obstacles on the road. The best reported visual acuity is 20/546.


These are the two most advanced examples of retinal implants. Other ongoing consortia like, Pixium,  Boston Retinal Implant or TSIC, Taiwan Sub-retinal Implant Consortium  are developing own implants.



(Cheng et al., 2017)

Challenges and Future

Despite of the few successful cases and  advances  made over the last decade, there are still challenges for retinal implants.. How are the effects to the chronic stimulation to both the function of the implants and to the remaining retinal neurons remain unclear. The resolution that implants can provided is another important issue. Eeven the best implant so far can only allow patients see objects vaguely. To increase the visual acuity, there are still a lot of engineering challenges to overcome. Other issues like the significant remodeling of neural network after photoreceptor degeneration or the lack of understanding of the interface between retina and the implants are the open questions to be answered.

Although there are difficulties to conquer, simple light sensitivity already help blind people greatly improve their quality of lives. More studies to the fundamental retinal neurosciences are going to help us explore the possibility and to break through the boundaries of technology. In the future, implants with better spatial and temporal resolution can be expected.


Current Status of Projects



(Cheng et al., 2017)

References

Cheng, D.L., Greenberg, P.B., and Borton, D.A. (2017). Advances in Retinal Prosthetic Research: A Systematic Review of Engineering and Clinical Characteristics of Current Prosthetic Initiatives. Curr Eye Res 42, 334-347.
Luo, Y.H., and da Cruz, L. (2014). A review and update on the current status of retinal prostheses (bionic eye). Br Med Bull 109, 31-44.
Stingl, K., Bartz-Schmidt, K.U., Besch, D., Braun, A., Bruckmann, A., Gekeler, F., Greppmaier, U., Hipp, S., Hoertdoerfer, G., Kernstock, C., et al. (2013). Artificial vision with wirelessly powered subretinal electronic implant alpha-IMS. Proceedings of the Royal Society B-Biological Sciences 280, 20130077.
Weiland, J.D., Cho, A.K., and Humayun, M.S. (2011). Retinal Prostheses: Current Clinical Results and Future Needs. Ophthalmology 118, 2227-2237.
Zrenner, E. (2013). Fighting blindness with microelectronics. Science translational medicine 5, 210ps216-210ps216.

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