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A flexible photoacoustic retinal prosthesis

Audrey Leong, Yueming Li, Thijs R. Ruikes, Julien Voillot, Yuhao Yuan, Guo Chen, Clémence Bradic, Arnaud Facon, Chakrya-Anna Chhuon, Corentin Joffrois, Gilles Tessier, Marion Cornebois, Julie Dégardin, Jean-Damien Louise, Ji-Xin Cheng, Chen Yang, Hélène Moulet, Serge Picaud

Nature Communications 2025 · 10.1038/s41467-025-67518-6

rodentex vivo tissuehealthyretinal degenerationinvasive electrophysiologyhistology molecularcerebral haemodynamics

Abstract

Retinal degenerative diseases of photoreceptors are a leading cause of blindness with no effective treatment. Retinal prostheses aim to restore sight by stimulating residual retinal cells. Here, we present a photoacoustic retinal stimulation technology. We designed a polydimethylsiloxane and carbon-based flexible film that converts near-infrared laser pulses into a localized acoustic field with 51-µm lateral resolution, allowing precise stimulation of mechanosensitive retinal cells. This photoacoustic stimulation robustly and locally modulated retinal ganglion cell activity in both wild-type and degenerated ex vivo rat retinae. In animals subretinally implanted with a millimeter-sized photoacoustic film, pulsed laser stimulation generated neural modulation along the visual pathway to the superior colliculus, as measured by functional ultrasound imaging. The biosafety of the film was confirmed by the absence of short-term adverse effects, while local thermal increases were measured below 1 °C. These findings demonstrate the potential of photoacoustic stimulation for high-acuity visual restoration in blind patients.

Abstract via europepmc.

Speciesrat (wild-type Long-Evans; P23H transgenic model of retinitis pigmentosa)
Subjects4, 4, 7swept animals
Sessions per subjectnot reported
Randomisednot reported
Blindingnot reported
Sham / controlother
Auditory controlnot reported
Readout timingboth
Anaesthesiaanaesthetised
Readoutsinvasive electrophysiology, histology molecular, cerebral haemodynamicsFunctional ultrasound imaging (fUSI) of relative cerebral blood volume in the contralateral superior colliculus; multi-electrode array (MEA) recordings of retinal ganglion cell firing; eye fundus imaging and optical coherence tomography (OCT) of the retina; immunohistochemistry (rods/cones, microglia, Müller glia).
Direction of effectexcitatoryPhotoacoustic stimulation predominantly increased retinal ganglion cell firing (92-93% of responding cells showed increased activity in both LE and P23H retinae) and produced increased relative cerebral blood volume (activation) in the contralateral superior colliculus, similar in amplitude and extent to visible-light stimulation of the retina.
Adverse eventsobservedNo retinal tearing or major inflammation was observed on OCT/fundus imaging after implantation. Local photoreceptor degeneration and reduced retinal thickness developed above the implant in LE rats (attributed to mechanical detachment from the RPE by the implant, not to acoustic stimulation), and activated microglia (and, in LE rats, Müller glia) were observed at the implantation site. Retinal thickness above the implant remained stable for up to 4 months in P23H rats. Local temperature increases at the film surface were below 1°C; estimated mechanical indices were below 0.03 (PDMS/CS/PDMS) and 0.1 (PDMS-CNT), within FDA ophthalmic ultrasound safety guidelines.

Exposures

Exposure 1: Photoacoustic stimulation of the retina (ex vivo RGC recordings in LE and P23H rat retinae; in vivo implanted LE/P23H rat retina with cSC readout)

Target: retina — “retina (retinal ganglion cells / mechanosensitive retinal cells), via subretinal photoacoustic film
Device: custom-built · PDMS/CS/PDMS and PDMS-CNT photoacoustic films (candle-soot/carbon-nanotube composite), driven by a 1030-nm pulsed laser

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)42,200✓✓
Pulse duration (ms)0.000036✓✓
Pulse repetition frequency (Hz)1,900, 3,500, 6,100swept✓✓
Duty cycle (%)0.025✓✓
Sonication duration (s)0.005, 0.03, 2swept?
Pressure and intensity, by domain
Free-field pressure (kPa)146.2✓✓
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatemeasurementsingle value
In-situ pressure (kPa)120, 50, 150swept✓✓
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)0.00006, 0.0009swept✓✓
Protocol, in the paper’s words

Ultrasound is generated photoacoustically: each ~4.2-ns, 1030-nm laser pulse is converted by the film into a single ~36-ns ultrasound pulse. Ex vivo: laser pulses delivered at frep=1.9 kHz (or 3.5 kHz) in a single burst of duration db=10 ms (standard) or swept db=5-30 ms per stimulation site. In vivo: the 1030-nm laser delivered eight 125-ms bursts during a 2-s train, repeated every 15 s, for 15 stimulations per recording (frep=6.1 kHz within each burst). Ex vivo pulse energy 10 µJ; in vivo laser power density 0.29±0.06 W/mm2 (PDMS/CS/PDMS) or 0.39±0.12 W/mm2 (PDMS-CNT).

Consistency checks: f0 out of range.

Flags from extraction

  • n_subjectsThe paper reports separate group sizes for different sub-experiments rather than one grand total: ex vivo LE retinae n=4 rats, ex vivo P23H retinae n=4 rats, in vivo biocompatibility P23H n=8, in vivo photoacoustic-stimulation LE n=7. These are not necessarily non-overlapping and are given as a list rather than summed.
  • exposures[0]Ultrasound is generated photoacoustically (laser-driven film), not by a conventional piezoelectric transducer; 'fundamental frequency' is the intrinsic acoustic centre frequency of the film (42.2 MHz) rather than a driven electrical frequency, and 'pulse duration'/'PRF'/'duty cycle' map onto the single ~36-ns photoacoustic pulse and laser repetition rate rather than a conventional TUS tone-burst; recorded with a flag given the unusual mapping onto the standard TUS timing fields.
  • exposures[0].timing.sonication_duration_sCombines the ex vivo swept burst-duration range (db=5-30 ms) with the very different in vivo train structure (eight 125-ms bursts within a 2-s train, repeated 15 times); these come from different experiments and are listed together for one target/frequency per the exposure-grouping rule.
  • exposures[0].free_field.pressure_kpa146.2 kPa is a hydrophone characterisation value at a non-stimulation laser condition (7 µJ/pulse, measured 0.9 mm from the film) and its measurement medium (water vs. tissue) is not explicitly stated; placed in free_field as the best-available characterisation value, distinct from the in-situ (at-target) stimulation pressures (0.05-0.15 MPa) reported elsewhere.
  • exposures[0].in_situ.ispta_w_cm2ISPTA values (below 0.06 and 0.9 mW/cm2) are stated as upper bounds ('below'), not exact values.
  • sham_typeControls used were stimulus-matched but non-photoacoustic (direct 1030-nm laser on the retina without the film; continuous 595-nm laser light on the retina), which does not match any listed sham_type category cleanly; coded as 'other'.
  • adverse_eventsEffects observed (photoreceptor thinning, microglial activation) are attributed by the authors to mechanical implantation rather than to the acoustic/photoacoustic stimulation itself.

Notes: Ultrasound in this study is generated by a laser-driven photoacoustic film rather than a conventional electrically-driven transducer; standard TUS timing/domain fields are populated on a best-effort basis (see flags).