Substantial and ongoing advances have been achieved in innovative therapeutic approaches for diabetic retinopathy (DR).The latest breakthroughs are highlighted in the following areas:
Nano-Drug Delivery Technologies Break Through the Blood-Retinal Barrier
Targeting the pain point of repeated intravitreal injections required by traditional anti-VEGF drugs,nano-drug delivery systems have achieved critical breakthroughs.
The TAT-iRGD dual-targeting nano eye drops developed by Chen Yanming’s teamcan deliver STING inhibitors across the blood-retinal barrier and suppress angiogenesis,reducing retinal leakage by 65% in animal models.
Chen et al. reported Pene/LQ015 eye drops (containing anti-VEGFA nanobodies and cell-penetrating peptides)that sustainably inhibit angiogenesis in cynomolgus monkeys with good safety and tolerance.
Nguyen et al. designed a biodegradable silicon nanoneedle subconjunctival patchfor sustained bevacizumab release over one year,reducing retinal neovascularization by 85% in rabbit models.
In addition, nanocarriers can efficiently deliver nucleic acids.Non-viral formulations enhance drug stability, enable precise targeting, and lower the risk of endophthalmitis,providing a new non-invasive, long-acting treatment pathway for DR.
Mesenchymal Stem Cell and Exosome Therapy
Mesenchymal stem cell-derived extracellular vesicles (MEVs) and their engineered exosomesoffer cell-free precision delivery strategies for DR treatment.
Guan et al. reported that CP05/KV11 dual-modified exosomes enable targeted anti-inflammatory drug delivery,increasing macular edema resolution by 58%.
Sun et al. confirmed that MEVs improve retinal function and inhibit photoreceptor apoptosis in db/db miceby delivering the deubiquitinase USP25 to suppress CRYAA ubiquitination.Modification with the photoreceptor-targeting peptide MH42 further enhanced repair efficiency.
Engineered extracellular vesicles feature high targeting efficiency, multi-molecule loading capacity, and low immunogenicity,providing an innovative direction for dual vascular-neural intervention in DR.
Explorations in Gene Therapy
Retinal gene therapy represented by RGX-314 (Sura-vec) has achieved milestone progress.
ABBV-RGX-314 uses an AAV8 vector to deliver anti-VEGF antibody fragments and inhibit abnormal angiogenesis.At the 2025 American Academy of Ophthalmology (AAO) Annual Meeting,2-year results from the Phase II ALTITUDE trial were reported:in the high-dose group, 100% of NPDR patients remained stable,and the risk of vision-threatening events was reduced by 89%,with no serious adverse events.
Clinical application of Luxturna®, the first approved ocular gene therapy,has validated the feasibility of this field.Innovations in delivery systems such as dual AAV vectors and lipid nanoparticles have further improved retinal targeting efficiency.
Challenges including viral vector immunogenicity and limited cell transduction efficiency still need to be overcome.Advances in CRISPR/Cas-mediated genome editing, prime editing, and combination with stem cell transplantationwill provide critical support for breaking through these bottlenecks.