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Optimization of stimulation parameters for epi-retinal implant based on biosafety consideration
Background: Optimizing stimulation protocol is essential for clinical application of retinal prosthesis. Elongating stimulation pulse width (~25ms /phase) has been proposed as an effective method to improve spatial resolution of epi-retinal implants. However, it is unknown whether longer stimulus pulse width will increase the risk of damaging the retina. In addition, with the advent of next generation retinal prosthesis featuring high-density microelectrode array, it is tempting to optimizing a single set of parameters for all electrodes instead of optimizing parameters of each electrode, but this approach raised biosafety concern. We sought to study the effect of stimulus pulse width on the response of retinal ganglion cells to electrical stimulation, and evaluate if the single parameter set approach was valid based on biosafety measures
Methods: We stimulated mouse retina using biphasic pulse waveform generated by chosen electrodes (single or a 3×3 assembly) from multiple microelectrode arrays, recorded their action potentials and performed spike sorting. We tested various stimulus intensity with two fixed pulse width: a short one for 1 millisecond per phase, and a long one for 25 milliseconds per phase.
All these assays were performed on two mouse models: the wildtype C57BL/6J mice and the photoreceptor degenerated rd10 mice. The action-potential-frequency vs stimulus amplitude profiles were plotted, and three parameters were extracted: the threshold (the lowest stimulus amplitude activating RGC units), safety-limit (stimulus amplitude that attenuated the firing rate to half of the maximum response), and the stimulation amplitude range (the difference between threshold and safety limit parameters).
Results: In single-electrode stimulation experiment, we found that on average 85% of the recorded units showed attenuated response to extreme stimulation; among those units, an average of 51% stopped responding during stimulation ramping and failed to recover after one-hour post-stimulation, indicating extreme stimulation can damage RGC units. Twenty-five-millisecond pulse stimulation significantly reduced safety-limit and stimulation-amplitude-range parameters of recorded RGC units compared to 1ms pulse stimulation.
Optimization of stimulation parameters for epi-retinal implant based on biosafety consideration
During stimulus amplitude ramping, the maximum proportion of responsive healthy RGC units was 51% on average in 25ms pulse condition, and 76% on average in 1ms pulse condition, indicating long pulse may inflict more strain on RGCs, and a significant amount of inappropriately stimulated RGCs always exist. The contrast of these proportions could be explained by the tight correlation between the threshold and safety-limit parameter in 25ms pulse condition. These results were corroborated by those from 3×3 array stimulation experiments.
Galanin-Like Peptide (GALP) (Human) - Antibody
H-026-51
PHOENIX PEPTIDE
50 μl
EUR 604.8
Peptide Histidine Methionine 27 (PHM-27) / Peptide Histidine Isoleucine (PHI) (Human) - Antibody
H-064-07
PHOENIX PEPTIDE
50 μl
EUR 238.68
GnRH Associated Peptide (GAP) (1-13) / GnRH Precursor Peptide (14-26) (Human)
029-03
PHOENIX PEPTIDE
500 μg
EUR 114.48
GnRH Associated Peptide (GAP) (1-24) / GnRH Precursor Peptide (14-37) (Human)
029-04
PHOENIX PEPTIDE
100 μg
EUR 114.48
GnRH Associated Peptide (GAP) (1-53) / GnRH Precursor Peptide (14-66) (Human)
029-05
PHOENIX PEPTIDE
20 μg
EUR 267.84
GnRH Associated Peptide (GAP) (25-53) / GnRH Precursor Peptide (38-66) (Human)
029-06
PHOENIX PEPTIDE
100 μg
EUR 114.48
Peptide YY (PYY) (3-36)-Gly (Human) - Antibody
H-059-08
PHOENIX PEPTIDE
100 μl
EUR 469.8
[Cys0]-Peptide YY (PYY) (3-19) (Human) - Antibody
H-059-16
PHOENIX PEPTIDE
100 μl
EUR 469.8
Gastrin Releasing Peptide (GRP) (Human) - Antibody
H-027-07
PHOENIX PEPTIDE
50 μl
EUR 238.68
[Cys20]-Peptide YY (PYY) (3-19) (Human) - Antibody
H-059-17
PHOENIX PEPTIDE
100 μl
EUR 469.8
Peptide YY (PYY) (Human) - Purified IgG Antibody
G-059-01
PHOENIX PEPTIDE
400 μg
EUR 438.48
Stresscopin Related Peptide (SRP) (Human) - Antibody
H-019-27
PHOENIX PEPTIDE
50 μl
EUR 604.8
Peptide YY (PYY) (Human) - EIA Kit
EK-059-01
PHOENIX PEPTIDE
96 wells
EUR 617.76
Peptide YY (PYY) (Human) - RIA Kit
RK-059-01
PHOENIX PEPTIDE
125 tubes
EUR 814.32
Galanin-Like Peptide (GALP) (36-60) (Human) - Antibody
H-026-55
PHOENIX PEPTIDE
50 μl
EUR 604.8
Galanin-Like Peptide (GALP) (Human)
026-51
PHOENIX PEPTIDE
100 μg
EUR 230.04
Anti-Angiogenic Peptide Library
L-008A
PHOENIX PEPTIDE
88 peptides
EUR 6067.44
T3 Peptide / Tumstatin (69-88) (Human)
016-50
PHOENIX PEPTIDE
100 μg
EUR 255.96
T7 Peptide / Tumstatin (74-98) (Human)
016-51
PHOENIX PEPTIDE
100 μg
EUR 255.96
Prolactin-Releasing Peptide-31 (PrRP-31) (Human) - Antibody
H-008-50
PHOENIX PEPTIDE
50 μl
EUR 604.8
Peptide YY (PYY) (3-36) (Human) - Purified IgG Antibody
G-059-02
PHOENIX PEPTIDE
200 μg
EUR 604.8
Gastrin Releasing Peptide (GRP) (Human)
027-07
PHOENIX PEPTIDE
200 μg
EUR 119.88
Peptide Histidine Methionine 27 (PHM-27) / Peptide Histidine Isoleucine (PHI) (Human) - Purified IgG Antibody
G-064-07
PHOENIX PEPTIDE
400 μg
EUR 438.48
Peptide Histidine Methionine 27 (PHM-27) / Peptide Histidine Isoleucine (PHI) (Human)
064-07
PHOENIX PEPTIDE
200 μg
EUR 114.48
Peptide YY (PYY) (1-36)-Gly (Human)
059-07
PHOENIX PEPTIDE
100 μg
EUR 295.92
Peptide YY (PYY) (3-36)-Gly (Human)
059-08
PHOENIX PEPTIDE
100 μg
EUR 282.96
Peptide YY (PYY) (2-36)-Gly (Human)
059-11
PHOENIX PEPTIDE
100 μg
EUR 267.84
Peptide YY (PYY) (4-36)-Gly (Human)
059-12
PHOENIX PEPTIDE
100 μg
EUR 267.84
Stresscopin Related Peptide (SRP) (Human)
019-27
PHOENIX PEPTIDE
100 μg
EUR 214.92
SHAAG Peptide / Chemokine (46-63) (Human)
072-32
PHOENIX PEPTIDE
100 μg
EUR 160.92
RFamide-Related Peptide 3 (RFRP-3) (Human) - Antibody
H-048-46
PHOENIX PEPTIDE
100 μl
EUR 604.8
Defensin I / Human Neutrophil Peptide-1 (HNP-1) (Human)
072-17
PHOENIX PEPTIDE
100 μg
EUR 370.44
Fractalkine Chemokine Domain peptide (41-52) (Human)
026-82
PHOENIX PEPTIDE
200 μg
EUR 160.92
Fractalkine Chemokine Domain peptide (53-60) (Human)
026-83
PHOENIX PEPTIDE
200 μg
EUR 135
Fractalkine Chemokine Domain peptide (60-71) (Human)
026-84
PHOENIX PEPTIDE
200 μg
EUR 160.92
Urotensin II Related Peptide (Human, Rat, Mouse) - Antibody
H-071-17
PHOENIX PEPTIDE
50 μl
EUR 604.8
Osteoblast Activating Peptide (OBAP) (Human)
055-52
PHOENIX PEPTIDE
100 μg
EUR 199.8
Human Proteome Signature Peptide Library
L-010
PHOENIX PEPTIDE
98 peptides
EUR 7804.08
C28 optimized peptide 15 Dimer (Human)
073-86
PHOENIX PEPTIDE
100 μg
EUR 420.12
Nesfatin-1-Like Peptide (NLP) (Human)
009-83
PHOENIX PEPTIDE
100 μg
EUR 469.8
APP 17mer peptide / APP770 (204-220) (Human)
018-74
PHOENIX PEPTIDE
100 μg
EUR 135
Galanin-Like Peptide (GALP) (Human) - Purified IgG Antibody
G-026-51
PHOENIX PEPTIDE
200 μg
EUR 604.8
C28 optimized peptide 15 Monomer (Human)
073-84
PHOENIX PEPTIDE
100 μg
EUR 258.12
Peptide YY (PYY) (3-36) (Human) - EIA Kit
EK-059-02
PHOENIX PEPTIDE
96 wells
EUR 617.76
Peptide YY (PYY) (3-36) (Human) - RIA Kit
RK-059-02
PHOENIX PEPTIDE
125 tubes
EUR 814.32
Peptide YY (PYY) (Human) - I-125 Labeled
T-059-01
PHOENIX PEPTIDE
10 μCi
EUR 1145.88
SHLP1 / Small Humanin-Like Peptide 1 (Human)
018-75
PHOENIX PEPTIDE
100 μg
EUR 263.52
SHLP2 / Small Humanin-Like Peptide 2 (Human)
018-76
PHOENIX PEPTIDE
100 μg
EUR 263.52
SHLP3 / Small Humanin-Like Peptide 3 (Human)
018-77
PHOENIX PEPTIDE
100 μg
EUR 422.28
SHLP4 / Small Humanin-Like Peptide 4 (Human)
018-78
PHOENIX PEPTIDE
100 μg
EUR 289.44
SHLP5 / Small Humanin-Like Peptide 5 (Human)
018-79
PHOENIX PEPTIDE
100 μg
EUR 316.44
SHLP6 / Small Humanin-Like Peptide 6 (Human)
018-80
PHOENIX PEPTIDE
100 μg
EUR 250.56
Gastrin Releasing Peptide (GRP) (Human) - Purified IgG Antibody
G-027-07
PHOENIX PEPTIDE
400 μg
EUR 438.48
Agouti-Related Peptide (AgRP) (83-132) amide (Human) - Antibody
H-003-53
PHOENIX PEPTIDE
50 μl
EUR 469.8
Galanin-Like Peptide (GALP) (36-60) (Human)
026-55
PHOENIX PEPTIDE
200 μg
EUR 177.12
Peptide Histidine Methionine 27 (PHM-27) / Peptide Histidine Isoleucine (PHI) (Human) - RIA Kit
RK-064-07
PHOENIX PEPTIDE
125 tubes
EUR 932.04
FGF23 (188-199 )optimized peptide 10 (Human)
073-88
PHOENIX PEPTIDE
100 μg
EUR 258.12
Stresscopin Related Peptide (SRP) (Human) - Purified IgG Antibody
G-019-27
PHOENIX PEPTIDE
200 μg
EUR 604.8
Prolactin-Releasing Peptide-31 (PrRP-31) (Human)
008-50
PHOENIX PEPTIDE
200 μg
EUR 199.8
Prolactin-Releasing Peptide-20 (PrRP-20) (Human)
008-51
PHOENIX PEPTIDE
200 μg
EUR 199.8
Peptide YY (PYY) (3-36) (Human) - FAM Labeled
FG-059-02A
PHOENIX PEPTIDE
1 nmol
EUR 336.96
Agouti-Related Peptide (AgRP) (25-51) (Human)
003-51
PHOENIX PEPTIDE
200 μg
EUR 129.6
Agouti-Related Peptide (AgRP) (54-82) (Human)
003-52
PHOENIX PEPTIDE
200 μg
EUR 129.6
Agouti-Related Peptide (AgRP) (25-82) (Human)
003-74
PHOENIX PEPTIDE
100 μg
EUR 497.88
Gastrin Releasing Peptide (GRP) (18-27) (Human)
027-41
PHOENIX PEPTIDE
200 μg
EUR 160.92
Seminal Plasma Inhibin-Like Peptide (Human)
034-03
PHOENIX PEPTIDE
200 μg
EUR 194.4
Gastrin Releasing Peptide (GRP) (1-16) (Human)
027-08
PHOENIX PEPTIDE
1 mg
EUR 177.12
Gastrin Releasing Peptide (GRP) (1-17) (Human)
027-42
PHOENIX PEPTIDE
200 μg
EUR 189
Peptide Histidine Methionine 27 (PHM-27) / Peptide Histidine Isoleucine (PHI) (Human) - FAM Labeled
FG-064-07A
PHOENIX PEPTIDE
1 nmol
EUR 336.96
Galanin-Like Peptide (GALP) (Human) - RIA Kit
RK-026-51
PHOENIX PEPTIDE
125 tubes
EUR 932.04
Prolactin-Releasing Peptide-31 (PrRP-31) (Human) - Purified IgG Antibody
G-008-50
PHOENIX PEPTIDE
400 μg
EUR 604.8
Galanin-Like Peptide (GALP) (36-60) (Human) - Purified IgG Antibody
G-026-55
PHOENIX PEPTIDE
200 μg
EUR 604.8
[Tyr0]-pro-Gastrin Releasing Peptide (GRP) (80-97) (Human) - Antibody
H-027-36
PHOENIX PEPTIDE
100 μl
EUR 370.44
Peptide YY (PYY) (3-36) (Human) - Biotin Labeled
B-059-02
PHOENIX PEPTIDE
10 μg
EUR 405
RFamide-Related Peptide 1 (RFRP-1) (Human)
048-42
PHOENIX PEPTIDE
500 μg
EUR 177.12
RFamide-Related Peptide 2 (RFRP-2) (Human)
048-44
PHOENIX PEPTIDE
500 μg
EUR 177.12
RFamide-Related Peptide 3 (RFRP-3) (Human)
048-46
PHOENIX PEPTIDE
500 μg
EUR 177.12
Gastrin Releasing Peptide (GRP) (Human) - EIA Kit
EK-027-07
PHOENIX PEPTIDE
96 wells
EUR 603.72
Gastrin Releasing Peptide (GRP) (Human) - RIA Kit
RK-027-07
PHOENIX PEPTIDE
125 tubes
EUR 932.04
Urotensin II Related Peptide (Human, Rat, Mouse)
071-17
PHOENIX PEPTIDE
200 μg
EUR 129.6
Peptide Histidine Methionine 27 (PHM-27) / Peptide Histidine Isoleucine (PHI) (Human) - I-125 Labeled
T-064-07
PHOENIX PEPTIDE
10 μCi
EUR 1145.88
T3 Peptide / Tumstatin (69-88) (Human) - FAM Labeled
FG-016-50A
PHOENIX PEPTIDE
1 nmol
EUR 469.8
T7 Peptide / Tumstatin (74-98) (Human) - FAM Labeled
FG-016-51A
PHOENIX PEPTIDE
1 nmol
EUR 469.8
Galanin-Like Peptide (GALP) (Human) - FAM Labeled
FG-026-51A
PHOENIX PEPTIDE
1 nmol
EUR 604.8
Stresscopin Related Peptide (SRP) (Human) - RIA Kit
RK-019-27
PHOENIX PEPTIDE
125 tubes
EUR 1341.36
Peptide YY (PYY) (3-36) (Human) - I-125 Labeled
T-059-02
PHOENIX PEPTIDE
10 μCi
EUR 1145.88
Peptide YY (PYY) (3-36) (Human) - Rhodamine Labeled
FR-059-02
PHOENIX PEPTIDE
1 nmol
EUR 405
Peptide YY (PYY) (3-36) (Human) - MagBead (Magnetic Bead Linked Antibody)
MB-059-02
PHOENIX PEPTIDE
1 ml
EUR 842.4
Gastrin Releasing Peptide-Gly (GRP-Gly) (Human)
027-37
PHOENIX PEPTIDE
100 μg
EUR 160.92
[Tyr0]-Agouti-Related Peptide (AgRP) (25-51) (Human)
003-72
PHOENIX PEPTIDE
100 μg
EUR 416.88
[Tyr0]-Agouti-Related Peptide (AgRP) (54-82) (Human)
003-73
PHOENIX PEPTIDE
100 μg
EUR 416.88
prepro-RFamide Related Peptide (RFRP) (56-92) amide (Human) - Antibody
H-048-54
PHOENIX PEPTIDE
100 μl
EUR 604.8
prepro-RFamide Related Peptide (RFRP) (115-131) amide (Human) - Antibody
H-048-55
PHOENIX PEPTIDE
50 μl
EUR 604.8
R3 (BDelta23-27) R / I5 Chimeric Peptide (Human)
035-66
PHOENIX PEPTIDE
100 μg
EUR 604.8
Nesfatin-1-Like Peptide(NLP) (Human) - RIA Kit
RK-009-83
PHOENIX PEPTIDE
125 tubes
EUR 980.64
7B2 Carboxyl-terminal (CT) peptide (Human, Porcine)
004-32
PHOENIX PEPTIDE
100 μg
EUR 160.92
Osteoblast Activating Peptide (OBAP) (Human) - EIA Kit
EK-055-52
PHOENIX PEPTIDE
96 wells
EUR 660.96
Osteoblast Activating Peptide (OBAP) (Human) - RIA Kit
RK-055-52
PHOENIX PEPTIDE
125 tubes
EUR 980.64
pro-Gastrin Releasing Peptide (GRP) (42-98) (Human)
027-34
PHOENIX PEPTIDE
100 μg
EUR 355.32
pro-Gastrin Releasing Peptide (GRP) (47-68) (Human)
027-35
PHOENIX PEPTIDE
100 μg
EUR 160.92
SHAAG Peptide / Chemokine (46-63) (Human) - Cy3 Labeled
FC3-072-32
PHOENIX PEPTIDE
1 nmol
EUR 587.52
SHAAG Peptide / Chemokine (46-63) (Human) - Cy5 Labeled
FC5-072-32
PHOENIX PEPTIDE
1 nmol
EUR 587.52
SHAAG Peptide / Chemokine (46-63) (Human) - FAM Labeled
FG-072-32A
PHOENIX PEPTIDE
1 nmol
EUR 267.84
Agouti-Related Peptide (AgRP) (71-132), Form C amide (Human) - Antibody
H-003-55
PHOENIX PEPTIDE
50 μl
EUR 604.8
Stresscopin Related Peptide (SRP) (Human) - FAM Labeled
FG-019-27A
PHOENIX PEPTIDE
1 nmol
EUR 537.84
prepro-Galanin-Like Peptide (GALP) (87-116) (Human)
026-54
PHOENIX PEPTIDE
200 μg
EUR 230.04
Urotensin II Related Peptide (Human, Rat, Mouse) - Purified IgG Antibody
G-071-17
PHOENIX PEPTIDE
200 μg
EUR 604.8
Peptide YY (PYY) (3-36) (Human) - Fluorescent EIA Kit
FEK-059-02
PHOENIX PEPTIDE
96 wells
EUR 660.96
Agouti-Related Peptide (AgRP) (83-132) amide (Human)
003-53
PHOENIX PEPTIDE
100 μg
EUR 316.44
[Leu(13C)6,(15N)-15,22]-Peptide YY (PYY) (3-36) (Human)
SIL-059-02
PHOENIX PEPTIDE
20 μg
EUR 1186.92
Gastrin Releasing Peptide (GRP) (14-27) (Human, Porcine)
027-16
PHOENIX PEPTIDE
500 μg
EUR 108
Prostate Specific Antigen (PSA) (243-261) / C-terminal PSA peptide (Human)
034-45
PHOENIX PEPTIDE
100 μg
EUR 199.8
[Tyr0]-RFamide-Related Peptide 1 (RFRP-1) (Human)
048-43
PHOENIX PEPTIDE
200 μg
EUR 177.12
[Tyr0]-RFamide-Related Peptide 2 (RFRP-2) (Human)
048-45
PHOENIX PEPTIDE
200 μg
EUR 177.12
[Tyr0]-RFamide-Related Peptide 3 (RFRP-3) (Human)
048-47
PHOENIX PEPTIDE
200 μg
EUR 177.12
Galanin-Like Peptide (GALP) (Human) - Rhodamine Labeled
FR-026-51
PHOENIX PEPTIDE
1 nmol
EUR 604.8
Parathyroid Hormone-Like Peptide (PLP) (140-173) (Human)
056-17
PHOENIX PEPTIDE
200 μg
EUR 129.6
SHAAG Peptide / Chemokine (46-63) (Human) - Biotin Labeled
B-072-32
PHOENIX PEPTIDE
10 μg
EUR 267.84
Prolactin-Releasing Peptide-31 (PrRP-31) (Human) - EIA Kit
EK-008-50
PHOENIX PEPTIDE
96 wells
EUR 603.72
Prolactin-Releasing Peptide-31 (PrRP-31) (Human) - RIA Kit
RK-008-50
PHOENIX PEPTIDE
125 tubes
EUR 932.04
Galanin-Like Peptide (GALP) (Human) - I-125 Labeled
T-026-51
PHOENIX PEPTIDE
10 μCi
EUR 1145.88
Osteoblast Activating Peptide (OBAP) (Human) - Cy3 Labeled
FC3-055-52
PHOENIX PEPTIDE
1 nmol
EUR 756
Osteoblast Activating Peptide (OBAP) (Human) - Cy5 Labeled
FC5-055-52
PHOENIX PEPTIDE
1 nmol
EUR 756
Osteoblast Activating Peptide (OBAP) (Human) - FAM Labeled
FG-055-52
PHOENIX PEPTIDE
1 nmol
EUR 537.84
Galanin-Like Peptide (GALP) (Human) - Western Blot Kit
WBK-026-51
PHOENIX PEPTIDE
1 kit
EUR 822.96
Peptide YY (PYY) (3-36) (Human) - Magnetic Bead RIA Kit
MRK-059-02
PHOENIX PEPTIDE
125 tubes
EUR 1061.64
Agouti-Related Peptide (AgRP) (83-132) amide (Human) - Purified IgG Antibody
G-003-53
PHOENIX PEPTIDE
400 μg
EUR 604.8
Gastrin Releasing Peptide (GRP) (Human) - I-125 Labeled
T-027-07
PHOENIX PEPTIDE
10 μCi
EUR 1145.88
SHAAG Peptide / Chemokine (46-63) (Human) - Rhodamine Labeled
FR-072-32
PHOENIX PEPTIDE
1 nmol
EUR 336.96
Peptide YY (PYY) (Human) - I-125 Labeled Purified IgG
T-G-059-01
PHOENIX PEPTIDE
10 μCi
EUR 1145.88
Galanin-Like Peptide (GALP) (36-60) (Human) - FAM Labeled
FG-026-55A
PHOENIX PEPTIDE
1 nmol
EUR 604.8
SHAAG Peptide / Chemokine (46-63) (Human) - I-125 Labeled
T-072-32
PHOENIX PEPTIDE
10 μCi
EUR 1145.88
prepro-Endothelin-1 (ET-1) Like Peptide (109-130) amide (Human)
023-11
PHOENIX PEPTIDE
100 μg
EUR 355.32
Peptide YY (PYY) (3-36) (Human) - Chemiluminescent EIA Kit
CEK-059-02
PHOENIX PEPTIDE
96 wells
EUR 660.96
Conclusion: Base on a biosafety measure (RGCs’ evoked firing rate in response to electrical stimulation), we proposed that longer stimulation pulse width could lead to reduced retinal response and thus highlighted the importance of carefully setting the stimulation amplitude in this case. Our results also suggested that optimizing a single set of parameters for all electrodes without individual tweaking always generated a significant amount of inappropriately stimulated RGCs, especially in the long pulse stimulation condition.