Electronic retinal prostheses for stimulating retinal neurons are promising for vision restoration. However, the rigid electrodes of conventional retinal implants can inflict damage on the soft retina tissue. They also have limited selectivity due to their poor proximity to target cells in the degenerative retina. Here we present a soft artificial retina (thickness, 10 μm) where flexible ultrathin photosensitive transistors are integrated with three-dimensional stimulation electrodes of eutectic gallium–indium alloy. Platinum nanoclusters locally coated only on the tip of these three-dimensional liquid-metal electrodes show advantages in reducing the impedance of the stimulation electrodes. These microelectrodes can enhance the proximity to the target retinal ganglion cells and provide effective charge injections (72.84 mC cm⁻²) to elicit neural responses in the retina. Their low Young’s modulus (234 kPa), owing to their liquid form, can minimize damage to the retina. Furthermore, we used an unsupervised machine learning approach to effectively identify the evoked spikes to grade neural activities within the retinal ganglion cells. Results from in vivo experiments on a retinal degeneration mouse model reveal that the spatiotemporal distribution of neural responses on their retina can be mapped under selective localized illumination areas of light, suggesting the restoration of their vision.

Human vision relies on photoreceptor cells in the outer retina that are sensitive to visible light. However, many people suffer from blindness due to retinal diseases that cause photoreceptor degeneration. Electrical stimulation of retinal neurons can recreate the action potentials associated with seeing that are generated by these cells. Here we report a thin artificial retina that can be adhered to the epiretinal surface and can convert near-infrared (NIR) light into electrical stimuli that selectively stimulate ganglion cells. The artificial retina consists of a NIR-sensitive phototransistor array and three-dimensional liquid metal micropillar electrodes. The liquid metal electrodes enhance proximity to retinal ganglion cells, providing effective charge injection while minimizing tissue damage, owing to their low Young’s modulus. Ex vivo studies demonstrate its biocompatibility, and in vivo studies using healthy and blind mice demonstrate perception of both visible and NIR light, as indicated by cortical recordings and behavioural tests. The retina could, in the future, be used to create a NIR visual channel in patients with photoreceptor degenerative blindness without interfering with their remaining natural vision.

MYCN amplification without concurrent RB1 mutations characterizes a rare yet highly aggressive subtype of retinoblastoma; however, its precise developmental origins and therapeutic vulnerabilities remain incompletely understood. Here, we modeled this subtype by lentiviral-mediated MYCN overexpression in human pluripotent stem cell-derived retinal organoids, revealing a discrete developmental window (days 70–120) during which retinal progenitors showed heightened susceptibility to transformation. Tumors arising in this period exhibited robust proliferation, expressed SOX2, and lacked CRX, consistent with origin from primitive retinal progenitors. MYCN-overexpressing organoids generated stable cell lines that reproducibly gave rise to MYCN-driven tumors when xenografted into immunodeficient mice. Transcriptomic profiling demonstrated that MYCN-overexpressing organoids closely recapitulated molecular features of patient-derived MYCN-amplified retinoblastomas, particularly through activation of MYC/E2F and mTORC1 signaling pathways. Pharmacological screening further identified distinct therapeutic vulnerabilities, demonstrating distinct subtype-specific sensitivity of MYCN-driven cells to transcriptional inhibitors (THZ1, Flavopiridol) and the cell-cycle inhibitor Volasertib, indicative of a unique oncogene-addicted state compared to RB1-deficient retinoblastoma cells. Collectively, our study elucidates the developmental and molecular mechanisms underpinning MYCN-driven retinoblastoma, establishes a robust and clinically relevant human retinal organoid platform, and highlights targeted transcriptional inhibition as a promising therapeutic approach for this aggressive pediatric cancer subtype.