Mohajeet Balveer Bhuckory

All Publications

• Residual photoreceptors affect the response of a degenerate retina to electrical stimulation. Proceedings of the National Academy of Sciences of the United States of America Ly, K., Bhuckory, M. B., Pham-Howard, D., Kochnev Goldstein, A., Jensen, N., Palanker, D. 2026; 123 (22): e2537064123

  Abstract

  Photovoltaic subretinal prosthesis can restore central vision in patients blinded by age-related macular degeneration with letter acuity matching its 100 µm pixel size. Improving resolution requires smaller pixels, but to still reach the target neurons, electric field should be less confined. However, wide-spreading field may engage adjacent photoreceptors and alter the visual perception. We studied the effects of residual photoreceptors on retinal responses to electrical stimulation using monopolar and bipolar photovoltaic arrays implanted subretinally in Long Evans rats with local photoreceptor loss, and compared that to RCS rats lacking all photoreceptors. Patterned retinal activation (880 nm, 0.5 to 10 ms) was assessed using visually evoked potentials under scotopic and photopic conditions, with and without the intravitreal injection of neurotransmitter blockers. Results were analyzed using a computational model of photoreceptor activation by various electric field configurations. We observed two mechanisms of photoreceptors engagement in electrical activation of the degenerate retina: 1) Dark-adapted photoreceptors near the implant can be simulated directly by a negative electric potential of the common return electrode along the edge of the array. 2) Light-adapted photoreceptors can reduce the stimulation threshold of bipolar cells within about 100 mm from the implant's edge. Both effects may lead to reduced perceptual uniformity. Bipolar pixels with local return electrodes generate better confined electric fields than monopolar arrays and thus are less affected by the nearby photoreceptors. However, even such implants should be placed a few hundred micrometers from the edge of scotoma to minimize the unintended percepts.

  View details for DOI 10.1073/pnas.2537064123

  View details for PubMedID 42201956

• Interferometric imaging of the reversible rhodopsin dynamics in the living rat eye. Nature communications Zhuo, Y., Li, H., Bhuckory, M., Pham-Howard, D., Palanker, D. 2025; 16 (1): 10730

  Abstract

  Vision begins with conformational changes in photopigments. The associated electrical signature, called an early receptor potential (ERP), in rods is limited to contribution of a small fraction of rhodopsin embedded in plasma membrane. Optoretinography (ORG), using phase-sensitive optical coherence tomography, detects nanoscale deformations of retinal cells associated with physiological processes. In previous ORG studies, focused primarily on cones, deformation related to ERP was largely obscured by osmotic swelling and long stimuli. Here, we demonstrate a robust electromechanical signature of photoisomerization in rods. A green flash induces a sub-millisecond contraction of the outer segments by hundreds of nanometers, while a subsequent UV flash reverts the activated molecules, producing an opposite response of similar magnitude. ORG surpasses the sensitivity of electrical methods by integrating the response across all the discs in rod outer segments and it opens the door to fundamental studies of visual transduction in-vivo and to more specific clinical diagnosis.

  View details for DOI 10.1038/s41467-025-65759-z

  View details for PubMedID 41315313

  View details for PubMedCentralID 1300410

• Reversible isomerization of rhodopsin imaged in a living eye with phase-sensitive OCT Zhuo, Y., Li, H., Bhuckory, M., Palanker, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2025

  View details for Web of Science ID 001568835200006

• Response of the degenerate retina to electrical stimulation is affected by residual photoreceptors Ly, K., Pham-Howard, D., Bhuckory, M., Goldstein, A., Jensen, N., Palanker, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2025

  View details for Web of Science ID 001560059200041

• Scaffold on photovoltaic prosthesis replicates the human subretinal debris layer for preclinical studies in rats Bhuckory, M., Shin, A., Ly, K., Mamchik, V., Jensen, N., Devaud, Q., Pham-Howard, D., Goldstein, A., Palanker, D. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2025

  View details for Web of Science ID 001560059200018

• Retinal thermal deformations measured with phase-sensitive optical coherence tomography in vivo. Light, science & applications Zhuo, Y., Bhuckory, M., Li, H., Hattori, J., Pham-Howard, D., Veysset, D., Ling, T., Palanker, D. 2025; 14 (1): 151

  Abstract

  Controlling the tissue temperature rise during retinal laser therapy is essential for predictable outcomes, especially at non-damaging settings. We demonstrate a method for determining the temperature rise in the retina using phase-sensitive optical coherence tomography (pOCT) in vivo. Measurements based on the thermally induced optical path length changes (ΔOPL) in the retina during a 10-ms laser pulse allow detection of the temperature rise with a precision less than 1 °C, which is sufficient for calibration of the laser power for patient-specific non-damaging therapy. We observed a significant difference in confinement of the retinal deformations between the normal and the degenerate retina: in wild-type rats, thermal deformations are localized between the retinal pigment epithelium (RPE) and the photoreceptors' inner segments (IS), as opposed to a deep penetration of the deformations into the inner retinal layers in the degenerate retina. This implies the presence of a structural component within healthy photoreceptors that dampens the tissue expansion induced by the laser heating of the RPE and pigmented choroid. We hypothesize that the thin and soft cilium connecting the inner and outer segments (IS, OS) of photoreceptors may absorb the deformations of the OS and thereby preclude the tissue expansion further inward. Striking difference in the confinement of the retinal deformations induced by a laser pulse in healthy and degenerate retina may be used as a biomechanical diagnostic tool for the characterization of photoreceptors degeneration.

  View details for DOI 10.1038/s41377-025-01798-x

  View details for PubMedID 40175338

  View details for PubMedCentralID PMC11965573

• Enhancing prosthetic vision by upgrade of a subretinal photovoltaic implant in situ. Nature communications Bhuckory, M. B., Monkongpitukkul, N., Shin, A., Kochnev Goldstein, A., Jensen, N., Shah, S. V., Pham-Howard, D., Butt, E., Dalal, R., Galambos, L., Mathieson, K., Kamins, T., Palanker, D. 2025; 16 (1): 2820

  Abstract

  In patients with atrophic age-related macular degeneration, subretinal photovoltaic implant (PRIMA) provided visual acuity up to 20/440, matching its 100 µm pixels size. Next-generation implants with smaller pixels should significantly improve the acuity. This study in rats evaluates removal of a subretinal implant, replacement with a newer device, and the resulting grating acuity in-vivo. Six weeks after the initial implantation with planar and 3-dimensional devices, the retina was re-detached, and the devices were successfully removed. Histology demonstrated a preserved inner nuclear layer. Re-implantation of new devices into the same location demonstrated retinal re-attachment to a new implant. New devices with 22 µm pixels increased the grating acuity from the 100 µm capability of PRIMA implants to 28 µm, reaching the limit of natural resolution in rats. Reimplanted devices exhibited the same stimulation threshold as for the first implantation of the same implants in a control group. This study demonstrates the feasibility of safely upgrading the subretinal photovoltaic implants to improve prosthetic visual acuity.

  View details for DOI 10.1038/s41467-025-58084-y

  View details for PubMedID 40118873

  View details for PubMedCentralID PMC11928519

• 3D electronic implants in subretinal space: Long-term follow-up in rodents. Biomaterials Bhuckory, M. B., Wang, B. Y., Chen, Z. C., Shin, A., Pham-Howard, D., Shah, S., Monkongpitukkul, N., Galambos, L., Kamins, T., Mathieson, K., Palanker, D. 2024; 311: 122674

  Abstract

  Clinical results with photovoltaic subretinal prosthesis (PRIMA) demonstrated restoration of sight via electrical stimulation of the interneurons in degenerated retina, with resolution matching the 100 μm pixel size. Since scaling the pixels below 75 μm in the current bipolar planar geometry will significantly limit the penetration depth of the electric field and increase stimulation threshold, we explore the possibility of using smaller pixels based on a novel 3-dimensional honeycomb-shaped design. We assessed the long-term biocompatibility and stability of these arrays in rats by investigating the anatomical integration of the retina with flat and 3D implants and response to electrical stimulation over lifetime - up to 32-36 weeks post-implantation in aged rats. With both flat and 3D implants, signals elicited in the visual cortex decreased after the day of implantation by more than 3-fold, and gradually recovered over the next 12-16 weeks. With 25 μm high honeycomb walls, the majority of bipolar cells migrate into the wells, while amacrine and ganglion cells remain above the cavities, which is essential for selective network-mediated stimulation of the retina. Retinal thickness and full-field stimulation threshold with 40 μm-wide honeycomb pixels were comparable to those with planar devices - 0.05 mW/mm2 with 10 ms pulses. However, fewer cells from the inner nuclear layer migrated into the 20 μm-wide wells, and stimulation threshold increased over 12-16 weeks, before stabilizing at about 0.08 mW/mm2. Such threshold is still significantly lower than 1.8 mW/mm2 with a previous design of flat bipolar pixels, confirming the promise of the 3D honeycomb-based approach to high resolution subretinal prosthesis.

  View details for DOI 10.1016/j.biomaterials.2024.122674

  View details for PubMedID 38897028

• On selectivity of neural stimulation with subretinal photovoltaic implants Goldstein, A., Jensen, N., Wang, B., Bhuckory, M., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2024

  View details for Web of Science ID 001313316205328

• Transcriptional and Translational Profiling of Reactive Muller Glia Following Cell-type specific Retinal Injury Ashouri, M., Bhuckory, M., Xia, X., Nahmou, M., Tsien, C., Huie, E., Li, B., Cameron, E., Wang, S., Palanker, D. V., Goldberg, J. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2024

  View details for Web of Science ID 001312227704300

• Mapping the retinal resistivity with electrical impedance tomography for modeling of retinal stimulation Shah, S., Goldstein, A., Chen, Z., Vasireddy, P., Bhuckory, M., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2024

  View details for Web of Science ID 001313316205324

• Replacement of a subretinal prosthesis with a higher-resolution array improves grating acuity in the same animal Bhuckory, M., Monkongpitukkul, N., Shin, A., Goldstein, A., Shah, S., Pham-Howard, D., Dalal, R., Galambos, L., Kamins, T., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2024

  View details for Web of Science ID 001313316205325

• Three-dimensional electro-neural interfaces electroplated on subretinal prostheses. Journal of neural engineering Butt, E., Wang, B. Y., Shin, A., Chen, Z. C., Bhuckory, M., Shah, S., Galambos, L., Kamins, T., Palanker, D., Mathieson, K. 2024

  Abstract

  High-resolution retinal prosthetics offer partial sight restoration to patients blinded by retinal degenerative diseases through electrical stimulation of remaining neurons. Decreasing pixel size enables increasing prosthetic visual acuity, as demonstrated in animal models of retinal degeneration. However, scaling down the size of planar pixels is limited by the reduced penetration depth of the electric field in tissue. We investigated 3-dimensional structures on top of photovoltaic arrays for enhanced penetration of the electric field, permitting higher resolution implants. Approach. 3D COMSOL models of subretinal photovoltaic arrays were developed to accurately quantify the electrodynamics during stimulation and verified through comparison to flat photovoltaic arrays. Models were applied to optimize the design of 3D electrode structures (pillars and honeycombs). Return electrodes on honeycomb walls vertically align the electric field with bipolar cells for optimal stimulation. Pillars elevate the active electrode improving proximity to target neurons. The optimized 3D structures were electroplated onto existing flat subretinal prostheses based on modelling results. Main results. Simulations demonstrate that despite exposed conductive sidewalls, charge mostly flows via high-capacitance sputtered Iridium Oxide films topping the 3D structures. The 24 µm height of honeycomb structures was optimized for integration with the inner nuclear layers cells in the rat retina, whilst 35 µm tall pillars were optimized for penetrating the debris layer in human patients. Implantation of released 3D arrays demonstrates mechanical robustness with histology demonstrating successful integration of 3D structures with the rat retina in-vivo. Significance. Electroplated 3D honeycomb structures produce vertically oriented electric fields, providing low stimulation thresholds, high spatial resolution, and contrast for pixel sizes down to 20 µm. Pillar electrodes offer alternatives for extending past debris layers. Electroplating of 3D structures is compatible with the fabrication process of flat photovoltaic arrays, enabling much more efficient stimulation. .

  View details for DOI 10.1088/1741-2552/ad2a37

  View details for PubMedID 38364290

• Cellular migration into a subretinal honeycomb-shaped prosthesis for high-resolution prosthetic vision. Proceedings of the National Academy of Sciences of the United States of America Bhuckory, M. B., Wang, B. Y., Chen, Z. C., Shin, A., Huang, T., Galambos, L., Vounotrypidis, E., Mathieson, K., Kamins, T., Palanker, D. 2023; 120 (42): e2307380120

  Abstract

  In patients blinded by geographic atrophy, a subretinal photovoltaic implant with 100 µm pixels provided visual acuity closely matching the pixel pitch. However, such flat bipolar pixels cannot be scaled below 75 µm, limiting the attainable visual acuity. This limitation can be overcome by shaping the electric field with 3-dimensional (3-D) electrodes. In particular, elevating the return electrode on top of the honeycomb-shaped vertical walls surrounding each pixel extends the electric field vertically and decouples its penetration into tissue from the pixel width. This approach relies on migration of the retinal cells into the honeycomb wells. Here, we demonstrate that majority of the inner retinal neurons migrate into the 25 µm deep wells, leaving the third-order neurons, such as amacrine and ganglion cells, outside. This enables selective stimulation of the second-order neurons inside the wells, thus preserving the intraretinal signal processing in prosthetic vision. Comparable glial response to that with flat implants suggests that migration and separation of the retinal cells by the walls does not cause additional stress. Furthermore, retinal migration into the honeycombs does not negatively affect its electrical excitability, while grating acuity matches the pixel pitch down to 40 μm and reaches the 27 μm limit of natural resolution in rats with 20 μm pixels. These findings pave the way for 3-D subretinal prostheses with pixel sizes of cellular dimensions.

  View details for DOI 10.1073/pnas.2307380120

  View details for PubMedID 37831740

• Electronic photoreceptors enable prosthetic visual acuity matching the natural resolution in rats. Nature communications Wang, B., Chen, Z. C., Bhuckory, M., Huang, T., Shin, A., Zuckerman, V., Ho, E., Rosenfeld, E., Galambos, L., Kamins, T., Mathieson, K., Palanker, D. 2022; 13 (1): 6627

  Abstract

  Localized stimulation of the inner retinal neurons for high-acuity prosthetic vision requires small pixels and minimal crosstalk from the neighboring electrodes. Local return electrodes within each pixel limit the crosstalk, but they over-constrain the electric field, thus precluding the efficient stimulation with subretinal pixels smaller than 55mum. Here we demonstrate a high-resolution prosthetic vision based on a novel design of a photovoltaic array, where field confinement is achieved dynamically, leveraging the adjustable conductivity of the diodes under forward bias to turn the designated pixels into transient returns. We validated the computational modeling of the field confinement in such an optically-controlled circuit by in-vitro and in-vivo measurements. Most importantly, using this strategy, we demonstrated that the grating acuity with 40mum pixels matches the pixel pitch, while with 20mum pixels, it reaches the 28mum limit of the natural visual resolution in rats. This method enables customized field shaping based on individual retinal thickness and distance from the implant, paving the way to higher acuity of prosthetic vision in atrophic macular degeneration.

  View details for DOI 10.1038/s41467-022-34353-y

  View details for PubMedID 36333326

• Pixel size limit of the PRIMA implants: from humans to rodents and back. Journal of neural engineering Wang, B. Y., Chen, Z. C., Bhuckory, M., Kochnev Goldstein, A., Palanker, D. 2022

  Abstract

  Retinal prostheses aim at restoring sight in patients with retinal degeneration by electrically stimulating the inner retinal neurons. Clinical trials with patients blinded by atrophic Age-related Macular Degeneration (AMD) using the PRIMA subretinal implant, a 2x2 mm array of 100µm-wide photovoltaic pixels, have demonstrated a prosthetic visual acuity closely matching the pixel size. Further improvement in resolution requires smaller pixels, which, with the current bipolar design, necessitates more intense stimulation.We examine the lower limit of the pixel size for PRIMA implants by modeling the electric field, leveraging the clinical benchmarks, and using animal data to assess the stimulation strength and contrast of various patterns. Visually evoked potentials measured in RCS rats with photovoltaic implants composed of 100µm and 75µm pixels were compared to clinical thresholds with 100µm pixels. Electrical stimulation model calibrated by the clinical and rodent data was used to predict the performance of the implant with smaller pixels.PRIMA implants with 75µm bipolar pixels under the maximum safe near-infrared (880nm) illumination of 8mW/mm2 with 30% duty cycle (10ms pulses at 30Hz) should provide a similar perceptual brightness as with 100µm pixels under 3mW/mm2 irradiance, used in the current clinical trials. Contrast of the Landolt C pattern scaled down to 75µm pixels is also similar under such illumination to that with 100µm pixels, increasing the maximum acuity from 20/420 to 20/315.Computational modelling defines the minimum pixel size of the PRIMA implants as 75µm. Increasing the implant width from 2 to 3 mm and reducing the pixel size from 100 to 75µm will nearly quadrupole the number of pixels, which should be very beneficial for patients. Smaller pixels of the same bipolar flat geometry would require excessively intense illumination, and therefore a different pixel design should be considered for further improvement in resolution.

  View details for DOI 10.1088/1741-2552/ac8e31

  View details for PubMedID 36044878

• Long-term integration of the retina with 3D implants: structure and function Wang, B., Bhuckory, M., Chen, Z., Shin, A., Galambos, L., Mathieson, K., Kamins, T., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401305225

• IFT88 Mediates Cilia-Associated Wound Repair in Retinal Pigment Epithelium Ning, K., Bhuckory, M., Kowal, T., Chen, M., Bansal, R., Palanker, D. V., Vollrath, D., Berbari, N., Mahajan, V. B., Hu, Y., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844437004307

• Retinal absorption measurements for laser therapy through interferometric imaging of the thermal expansion Veysset, D., Zhuo, Y., Hattori, J., Bhuckory, M., Pandiyan, V., Sabesan, R., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844401303047

• 3-dimensional subretinal prosthesis with single-cell resolution Bhuckory, M., Chen, Z., Shin, A., Wang, B., Galambos, L., Kamins, T., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022

  View details for Web of Science ID 000844437006274

• Retinal integration with a subretinal honeycomb-shaped prosthesis Bhuckory, M., Chen, Z., Wang, B., Huang, T., Galambos, L., Shin, A., Kamins, T., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690761600452

• Dynamic Transcriptional and Translational Profiling of Reactive Muller Glia Following Retinal Injury Ashouri, M., Bhuckory, M., Nahmou, M., Hay, S., Knasel, C. M., Cameron, E. G., Wang, S., Palanker, D. V., Goldberg, J. L. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690761100769

• Optically configurable confinement of electric field with photovoltaic retinal prosthesis Chen, Z., Wang, B., Bhuckory, M., Huang, T., Galambos, L., Mathieson, K., Kamins, T., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690761600406

• Subretinal monopolar photovoltaic arrays provide pixel size-independent stimulation threshold and 40 mu m resolution under spatiotemporal modulation Wang, B., Bhuckory, M., Chen, Z., Huang, T., Galambos, L., Mathieson, K., Kamins, T., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2021

  View details for Web of Science ID 000690761600405

• Vertical-junction photodiodes for smaller pixels in retinal prostheses. Journal of neural engineering Huang, T. W., Kamins, T. n., Chen, Z. C., Wang, B. Y., Bhuckory, M. n., Galambos, L. n., Ho, E. n., Ling, T. n., Afshar, S. n., Shin, A. n., Zuckerman, V. n., Harris, J. S., Mathieson, K. n., Palanker, D. n. 2021

  Abstract

  Objective.To restore central vision in patients with atrophic age-related macular degeneration, we replace the lost photoreceptors with photovoltaic pixels, which convert light into current and stimulate the secondary retinal neurons. Clinical trials demonstrated prosthetic acuity closely matching the sampling limit of the 100 μm pixels, and hence smaller pixels are required for improving visual acuity. However, with smaller flat bipolar pixels, the electric field penetration depth and the photodiode responsivity significantly decrease, making the device inefficient. Smaller pixels may be enabled by (1) increasing the diode responsivity using vertical p-n junctions and (2) directing the electric field in tissue vertically. Here, we demonstrate such novel photodiodes and test the retinal stimulation in a vertical electric field.Approach.Arrays of silicon photodiodes of 55, 40, 30, and 20 μm in width, with vertical p-n junctions, were fabricated. The electric field in the retina was directed vertically using a common return electrode at the edge of the devices. Optical and electronic performance of the diodes was characterized in-vitro, and retinal stimulation threshold measured by recording the visually evoked potentials (VEPs) in rats with retinal degeneration.Main results.The photodiodes exhibited sufficiently low dark current (<10 pA) and responsivity at 880 nm wavelength as high as 0.51 A/W, with 85% internal quantum efficiency, independent of pixel size. Field mapping in saline demonstrated uniformity of the pixel performance in the array. The full-field stimulation threshold was as low as 0.057±0.029 mW/mm2with 10 ms pulses, independent of pixel size.Significance.Photodiodes with vertical p-n junctions demonstrated excellent charge collection efficiency independent of pixel size, down to 20 μm. Vertically-oriented electric field provides a stimulation threshold that is independent of pixel size. These results are the first steps in validation of scaling down the photovoltaic pixels for subretinal stimulation.

  View details for DOI 10.1088/1741-2552/abe6b8

  View details for PubMedID 33592588

• Titration for selective RPE therapy using a continuous line scanning laser Bhuckory, M., Flores, T., Shao, X., Dalal, R., Palanker, D. V. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019

  View details for Web of Science ID 000488800700240