MEMS technology has been attracting increasing attention in several medical fields for its possible applications in curing diseases, which were considered intractable until few years ago. A typical application, as example, regards the MEMS based cochlear implant, which is meant to give hearing to deaf people through a wireless communication device. Moreover, MEMS accelerometer are widely applied to detect movement, heat flow, skin temperature, heart rate, etc...
Among all these applications, one in particular attracts the attention of researchers: the microchip retinal implant. Extended studies have been conducted in several places of the world (USA, Japan, Australia, etc…) in order to develop a microchip able to stimulate damaged retinal cells. This is very important for patients affected by Retinitis Pigmentosa (RP) and Age related Macular Degeneration (AMD).
In this research, the structure of the eye and the basic principle of the eye’s view will be investigated. The focus will be in particular on the function of the retina on the process of sight and the characteristics of the macula, the part of the retina, which gives the highest resolution for the images. The possible diseases and abnormal retinal conditions will also be briefly considered, especially the aforementioned Retinitis Pigmentosa and Age related Macular Degeneration.
In the second part of the project, the possible approaches to cure the retinal degeneration will be analyzed (i.e.: epiretinal and subretinal implant). In particular the study will focus on the microdevices applied in both the aforementioned approaches. On one side the epiretinal system is based on a retina encoder, a telemetry link and a stimulator device. On the other side the subretinal implant is based on a silicon microchip of 2mm diameter, which contains microscopic solar cells called microphotodiodes. These are designed to convert the light energy from images into electrochemical impulses that stimulate the remaining functional cells of the retina in patients with AMD and RP. Moreover, it is designed to produce visual signals similar to those produced by the photoreceptor layer in order to subsequently induce biological signals in the remaining functional retinal cells.
The research will also point out the main aspects in the microfabrication of these microchips and the possible alternatives in the process. Another important issue is the biocompatibility of the various component involved in the fabrication, with a particular concern for the biocompatibility of silicon.
Finally, some important results from the application of these new techniques will be addressed. In fact, pre-clinical laboratory testing showed that animal models with the retinal implant responded to light stimuli with electrical signals and sometimes brain wave signals. The induction of these biological signals indicated that visual responses had occurred. Besides, the subretinal device has been implanted in some patients with RP to study its safety and feasibility in treating retinal vision loss. Until now no patient has shown signs of implant rejections, inflammation or other problems.
The human eye is composed by several parts but the most important is definitely the retina, which converts light information into neural electrical signals. These signals are transported to the visual cortex of the brain by the optic nerve. The visual cortex then decodes the neural signals into a meaningful image.
The retina is composed of approximately 126 million photoreceptors (size: 2-3 m), which provide an analog electronic signal to the attached bipolar neural cell layer. The bipolar cells convert the signal into electrical pulse train. Signal processing and convergence is performed in all neural cell layers comprising horizontal cell, bipolar cells, amacrine cells and ganglion. Approximately one million axons of the ganglion cells form the optic nerve, which extends into the visual cortex of the brain. The light passes through the eye and through the 200 µm thin retina neural layer before reaching the photoreceptors (Fig. 1 in next page).
Fig. 1: Structure of the retina.
This description of the retina is definitely simplified, in fact there are many interneurons in the central part of the retina section between the photoreceptors and the ganglion cells. However, the concepts introduced can adequately support the scope of this research.
A group of diseases that may affect the retina is the Retinitis Pigmentosa (RP) and the Age-related Macular Degeneration (AMD). These diseases are characterised by a gradual breakdown and degeneration of the photoreceptor cells. Depending on which type of cell is mainly affected
, the symptoms vary, and include night blindness, lost peripheral vision (tunnel vision) and loss of the ability to discriminate colour. Symptoms of RP are most often recognised in adolescents and young adults
, with progression of the disease usually continuing throughout the individual's life. The rate of progression and degree of visual loss are variable.
So far, there is no known cure for RP. However, intensive research is currently under way to discover the cause, prevention and treatment. At this time, RP researchers have identified a first step in managing RP: certain doses of vitamin A have been found to slightly slow the progression of the disease in some individuals. Researches have also found some of the genes that cause RP.
There are other inherited retinal degenerative diseases that share some of the clinical symptoms of RP. Some of these conditions are complicated by other symptoms besides the loss of vision. The most common of these is Usher Syndrome
, which causes both hearing and vision loss. Other rare syndromes that researchers are studying include Bardet-Biedl syndrome
, Best Disease
, Leber Congenital Amaurosis
and Stargardt Disease
pproaches to cure retinal diseases
In order to cure retinal diseases the possible approaches are the subretinal implant and the epiretinal implant. These two methods differ because they substitute different physiological functions.
An epiretinal implant stimulates directly the ganglion cells. The device generates spike trains at defined sites of the retina. The epiretinal device does not rely on the natural data processing of the neural compartments in the retina. Hence, the epiretinal approach requires an encoder for mapping visual patterns onto pulse trains as inputs for electronic stimulation.
A subretinal implant is meant to replaces the degenerated photoreceptors with photodiodes and electrodes. Hence, the technical implant must provide an analog signal to the adjacent neural layers. In this case the neural retina must be partly intact and it must be able to maps the visual pattern into pulse trains. The signals are processed and converged in the functional neural layers of the retina before they are transmitted through the optic nerve into the visual cortex.
THE EPIRETINAL MICROIMPLANT
The epiretinal device introduced previously is composed by three major elements: the retina encoder, a telemetry link for power and data transmission, and the implantable stimulator device (Fig. 2). The image sensor, the implantable power and data receiver as well as the stimulator are fabricated using standard CMOS technology.
Fig. 2: The epiretinal system and its 3 functional units.