News Column

"Method for Identification of Retinal Cell Types Intrinsic Properties" in Patent Application Approval Process

May 22, 2014



By a News Reporter-Staff News Editor at Politics & Government Week -- A patent application by the inventors Chichilnisky, Eduardo-Jose (Cardiff, CA); Jepson, Lauren (San Diego, CA); Greschner, Martin (Oldenburg, DE), filed on March 19, 2012, was made available online on May 8, 2014, according to news reporting originating from Washington, D.C., by VerticalNews correspondents.

This patent application is assigned to Salk Institute For Biological Studies.

The following quote was obtained by the news editors from the background information supplied by the inventors: "A retinal prosthesis is a device implanted in the eyes of blind patients to stimulate retinal neurons that have survived degeneration, causing those neurons to transmit artificial visual signals to the brain. If the artificial visual signals closely mimic natural retinal signals, the device could provide useful artificial vision to millions of blind patients. A major limitation of prototype prostheses now in clinical trials is that they stimulate many neurons of different types indiscriminately and simultaneously. This is problematic because in the normal retina, roughly 20 different types of retinal ganglion cells send different types of visual information to diverse targets in the brain, and these cell types are intermingled in the retina. Four major ganglion cell types (ON-midget, OFF-midget, ON-parasol, OFF-parasol) form about 70% of the visual signals conveyed to the brain and supply neural signals to brain areas responsible for high resolution vision. In normal vision, these cells produce different signals at different times. For example, ON and OFF cells respond to increments and decrements of light, respectively; midget cells exhibit slower and less transient responses than parasol cells. Thus, current prostheses that activate different cell types simultaneously and indiscriminately produce abnormal retinal signals. Such a device is of limited utility to the patient."

In addition to the background information obtained for this patent application, VerticalNews journalists also obtained the inventors' summary information for this patent application: "Provided herein are methods for identifying cell clusters or cell types of retinal cells at one or more areas of a retina by recording corresponding electrical signals. Based on the recorded signals, cell types or clusters are identified, and electrical stimuli are applied based on the identified cell types. In some embodiments, temporal spike patterns of the cells are recorded, and cell spatio-temporal voltage patterns and spike pattern cross-correlations are estimated. In some examples, cells types are determined based on clustering with cells having similar electrical properties. While inherent electrical signals produced by cells can be analyzed to establish cell type, in some examples, characteristic retinal cell electrical signals are produced in response to an applied electrical or optical stimulus.

"Retinal stimulus apparatus comprise a signal conditioner configured to receive an electrical signal associated with a retinal area to produce a conditioned electrical signal. A signal analyzer is coupled to the signal conditioner and configured to associate the at least one retinal area with at least one retinal cell type or cluster based on the conditioned electrical signal. In some embodiments, the apparatus further includes a memory configured to store an indication of the retinal cell type, an electrode array and/or a retinal stimulus generator. In some instances, the signal conditioner is configured to receive a plurality of electrical signals associated with respective retinal areas and produce corresponding conditioned electrical signals, and the signal analyzer is configured to associate the retinal areas with associated retinal cells types based on the conditioned electrical signal. In some embodiments, the apparatus further comprises an electrode array that includes a plurality of electrodes configured to be electrically coupled to respective retinal areas and deliver corresponding electrical signals to the signal conditioner, and the signal conditioner includes a plurality of electrode amplifiers coupled to respective electrodes. In some embodiments, the signal conditioner includes a plurality of electrode switches configured to selectively couple an associated electrode to the signal analyzer. In particular examples, the apparatus further includes a retinal stimulus generator configured to provide retinal interrogation signals to the plurality of electrodes, and the conditioned electrical signals received by the signal analyzer are based on the retinal interrogation signals. In some examples, the apparatus further includes an optical stimulus generator configured so that the electrical signals associated with the retina are based an optical stimulus signal. In some embodiments, the signal conditioner includes a plurality of electrode switches configured to selectively couple an associated electrode to the signal analyzer.

"In other examples, a retinal prosthesis includes an electrode array configured to be coupled to a retina, and a retinal signal generator configured to provide electrical signals to respective electrodes of the electrode array based on retinal cell types associated with the electrodes. In some embodiments, the retinal prosthesis further includes a memory coupled to the electrical signal generator, an image sensor coupled to the retinal signal generator and/or a signal analyzer coupled to the electrode array. In some examples, the memory is configured to store indicators of the retinal cell types associated with the electrodes. In one non-limiting example, the memory is configured to store indicators of two or more retinal cell types associated with at least some of the electrodes. In further examples, the retinal prosthesis includes an image sensor coupled to the retinal signal generator such that the electrical signals provided to the respective electrodes are based on an image signal provided by the image sensor. In some cases, signals provided to electrodes are not necessarily the same as image intensities, and image sensor signals are processed in order to establish suitable electrode signals. In other representative embodiments, the retinal prosthesis further includes a signal analyzer coupled to the electrode array so as to receive electrical signals from portions of the retina and identify retinal cell types associated with the portions. In one non-limiting example, the signal analyzer is configured to store indications of the identified cell types in the memory.

"The foregoing and other objects, features, and advantages will become more apparent from the following detailed description, which proceeds with reference to the accompanying figures.

BRIEF DESCRIPTION OF THE DRAWINGS

"FIG. 1 is a block diagram of a representative apparatus for recording electrical signals of retinal cells, determining cell types at a plurality of electrode locations, and applying cell-type specific retinal stimuli.

"FIG. 2 is a block diagram of a method for identifying retinal cell types.

"FIG. 3 is a block diagram of a representative retinal prosthesis.

"FIG. 4 is a block diagram of a representative retinal database that includes a retinal cell type database.

"FIG. 5 is a set of graphs showing spike patterns of primate retinal ganglion measured using auto-correlations. Each panel shows the auto-correlation of the spikes of a number of cells of a particular type, recorded simultaneously from primate retina. Each trace indicates the normalized average firing rate of a cell as a function of time relative to the occurrence of a spike in the cell at time zero. Each cell type exhibits a characteristic auto-correlation waveform; traces are similar for all cells of one type (within a panel) and different for cells of different types (different panels). Arrows and lines indicate some but not all features of auto-correlation that are clearly distinct between cell types.

"FIGS. 6A-6B are electrical images associated with retinal areas, and FIG. 6C includes associated voltage waveforms. FIG. 6A includes black dots corresponding to an electrical image showing the amplitude of an average voltage obtained on 512 electrodes in a hexagonal array. Numbered dots (shaded) show electrodes for which corresponding average voltage traces are shown in FIG. 6C. Trace 1 is typical of a recording from a cell body. Trace 2 is typical of dendrites around a cell body. Traces 3-5 are typical axon waveforms. Time offsets in traces 3-5 show that the voltage waveform propagates from electrode 1 toward electrode 5. Conduction velocity of this propagation is roughly 1 msec. FIG. 6B shows electrical image for two ganglion cells (black dots) and their light-sensitive regions (circled) overlapping the cell body and dendrite locations, indicating that normal light-sensitive regions can be obtained from the electrical image.

"FIGS. 7A-7C are a series of graphs showing cross-correlations between identified cell types in primate retina. Each cross-correlation function indicates the spike rate of one cell as a function of time relative to the occurrence of a spike in the second cell. FIG. 7A shows cross-correlations between ON-parasol cells revealing a two-peaked structure reflecting its origin in gap junctions, whereas the cross-correlation function in OFF-parasol cells exhibits only one peak. FIG. 7B shows a negative correlation between ON-midget and OFF-midget cells that differs from a positive correlation between OFF-parasol and OFF-midget cells. FIG. 7C shows that degree of correlation as a function of distance between cells declines more rapidly for parasol-midget cell pairs than parasol-parasol cell pairs, and the maximum correlation between these cell types also differs. (Greschner et al, J. Physiol. 589:75, 2010).

"FIGS. 8A-8B are plots showing cell type clustering and identification using intrinsic properties. (A) In a primate retina, ON-parasol, OFF-parasol, ON-midget and OFF-midget cells (bottom right group, top right group, bottom left group, and top left group, respectively) were identified based on light responses. See Field et al., J Neurosci 27:13261, 2007. The first principal component of the auto-correlation, and the axon conduction velocity, are shown for each cell. Clustering of cell types indicates that these intrinsic properties can be used for identification. However, other aspects of auto-correlation, cross-correlation and waveform can be used as well. (B) Identification with auto-correlation in adult, degenerated P23H rat reveals three cell types in one recording indicating the utility of the method in degenerated retina."

URL and more information on this patent application, see: Chichilnisky, Eduardo-Jose; Jepson, Lauren; Greschner, Martin. Method for Identification of Retinal Cell Types Intrinsic Properties. Filed March 19, 2012 and posted May 8, 2014. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.html&r=1636&p=33&f=G&l=50&d=PG01&S1=20140501.PD.&OS=PD/20140501&RS=PD/20140501

Keywords for this news article include: Cells, Neurons, Prosthetics, Medical Devices, Clinical Trials and Studies, Salk Institute For Biological Studies.

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Source: Politics & Government Week


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