Electronic retinal prostheses seek to restore sight in patients with retinal degeneration by delivering pulsed
electric currents to retinal neurons via an array of microelectrodes. Most implants use inductive or optical transmission
of information and power to an intraocular receiver, with decoded signals subsequently distributed to retinal electrodes
through an intraocular cable. Surgical complexity could be minimized by an "integrated" prosthesis, in which both
power and data are delivered directly to the stimulating array without any discrete components or cables. We present
here an integrated retinal prosthesis system based on a photodiode array implant. Video frames are processed and
imaged onto the retinal implant by a video goggle projection system operating at near-infrared wavelengths (~ 900 nm).
Photodiodes convert light into pulsed electric current, with charge injection maximized by specially optimized series
Prostheses of three different pixel densities (16 pix/mm<sup>2</sup>, 64 pix/mm<sup>2</sup>, and 256 pix/mm<sup>2</sup>) have been designed,
simulated, and prototyped. Retinal tissue response to subretinal implants made of various materials has been investigated
in RCS rats. The resulting prosthesis can provide sufficient charge injection for high resolution retinal stimulation
without the need for implantation of any bulky discrete elements such as coils or tethers. In addition, since every pixel
functions independently, pixel arrays may be placed separately in the subretinal space, providing visual stimulation to a
larger field of view.
Electronic retinal prostheses represent a potentially effective approach for restoring some degree of sight in blind
patients with retinal degeneration. Functional restoration of sight would require hundreds to thousands of electrodes
effectively stimulating remaining neurons in the retina. We present a design of an optoelectronic retinal prosthetic
system having 3mm diameter retinal implant with pixel sizes down to 25 micrometers, which allows for natural eye
scanning for observing a large field of view, as well as spatial and temporal processing of the visual scene to optimize
the patient experience. Information from a head mounted video camera is processed in a portable computer and
delivered to the implanted photodiode array by projection from the LCD goggles using pulsed IR (810 nm) light. Each
photodiode converts pulsed light (0.5 ms in duration) into electric current with efficiency of 0.3 A/W using common bi-phasic
power line. Power is provided by the inductively-coupled RF link from the coil on the goggles into a miniature
power supply implanted between the sclera and the conjuctiva, and connected to subretinal implant with a thin 2-wire
3-dimensional structures in the subretinal prosthesis induce retinal migration and thus ensure close proximity between
stimulating electrodes and the target retinal neurons. Subretinal implantations of the 3-dimentional pillar and chamber
arrays in RCS rats with 2 and 6 week follow-up demonstrate achievement of intimate proximity between the stimulation
cites and the inner nuclear layer. In some instances formation of a fibrotic seal has been observed.
A major obstacle in applying gene therapy to clinical practice is the lack of efficient and safe gene delivery
techniques. Viral delivery has encountered a number of serious problems including immunological reactions and
malignancy. Non-viral delivery methods (liposomes, sonoporation and electroporation) have either low efficiency in-vivo
or produce severe collateral damage to ocular tissues.
We discovered that tensile stress greatly increases the susceptibility of cellular membranes to electroporation.
For synchronous application of electric field and mechanical stress, both are generated by the electric discharge itself. A pressure wave is produced by rapid vaporization of the medium. To prevent termination of electric current by the vapor cavity it is ionized thus restoring its electric conductivity. For in-vivo experiments with rabbits a plasmid DNA was injected into the subretinal space, and RPE was treated trans-sclerally with an array of microelectodes placed outside the eye. Application of 250-300V and 100-200 μs biphasic pulses via a microelectrode array resulted in efficient
transfection of RPE without visible damage to the retina.
Gene expression was quantified and monitored using bioluminescence (luciferase) and fluorescence (GFP) imaging. Transfection efficiency of RPE with this new technique exceeded that of standard electroporation by a factor
10,000. Safe and effective non-viral DNA delivery to the mammalian retina may help to materialize the enormous
potential of the ocular gene therapy. Future experiments will focus on continued characterization of the safety and
efficacy of this method and evaluation of long-term transgene expression in the presence of phiC31 integrase.
Electronic retinal prostheses represent a potentially effective approach for restoring some degree of
sight in blind patients with retinal degeneration. However, levels of safe electrical stimulation and the
underlying mechanisms of cellular damage are largely unknown. We measured the threshold of cellular
damage as a function of pulse duration, electrode size, and number of pulses to determine the safe range of
stimulation. Measurements were performed in-vitro on embryonic chicken retina with saline-filled glass
pipettes for stimulation electrodes. Cellular damage was detected using Propidium Iodide fluorescent
staining. Electrode size varied from 115μm to 1mm, pulse duration from 6μs to 6ms, and number of pulses
from 1 to 7,500. The threshold current density was independent of electrode sizes exceeding 400μm. With
smaller electrodes the current density was scaling reciprocal to the square of the pipette diameter, i.e. acting
as a point source so that the damage threshold was determined by the total current in this regime. The
damage threshold current measured with large electrodes (1mm) scaled with pulse duration as t<sup>-0.5</sup>, which is
characteristic of electroporation. For repeated electrical pulsed exposure on the retina the threshold current
density varied between 0.059 A/cm2 at 6ms to 1.3 A/cm2 at 6μs. The dynamic range of safe stimulation,
i.e. the ratio of damage threshold to stimulation threshold was found to be duration-dependent, and varied
from 10 to 100 at pulse durations varying between 10μs to 10ms. Maximal dynamic range of 100 was
observed near 1ms pulse durations.