A 3D CELLULAR MODEL OF EARLY DIABETIC RETINOPATHY

Only validated model of early-stage DR – Rodents never develop pre-vascular DR, whereas PRISM reproduces the human neuro-inflammatory phase with -50 % ganglion/amacrine survival, 2 × VEGF / IL-1β, 1.75 × MCP-1 and 1.6 × ROS (patent data; n = 3 differentiations). Weeks instead of months – high-glucose challenge delivers decision-making data in < 3 weeks, versus 12–16-week diabetic mouse protocols that model only late vascular damage. Multi-endpoint in a single assay – High-content imaging, qPCR, ELISA and Western blot run on the same organoid plate, providing parallel efficacy and mechanism read-outs. Animal-free & regulator aligned – Fully human 3-D system meets the direction of FDA Modernization Act 2.0 and EMA 3R roadmap, lowering ethical burden and translational risk. Ready with commercial hiPSC lines – Uses off-the-shelf cell sources; no patient tissue or complex ethics approvals needed, simplifying tech transfer and future scale-up. Phenotypic hit & lead screening – Rank neuro-protective or anti-inflammatory small-molecule libraries directly in human retinal tissue. Mechanism-of-action validation – Quantify pathway modulation (mTOR, ROS, cytokines) to confirm target engagement before in-vivo studies. Gene-therapy efficacy testing – Assess AAV or CRISPR constructs for rescue of ganglion/amacrine degeneration and inflammatory biomarkers. Retina-specific safety profiling – Detect early neuro-toxicity or pro-inflammatory off-targets that 2-D cultures and rodent models miss. Biomarker discovery support – Generate human retinal RNA/protein signatures to guide clinical translation and patient-stratification efforts.