ArticleStem cell research & therapy2026
Chitosan-rapamycin carbon dots rejuvenate autologous Sca-1⁺ stem cells paracrine function for neuroprotection in normal tension glaucoma.
Article in Stem cell research & therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundNormal tension glaucoma (NTG) causes progressive retinal ganglion cell (RGC) loss without elevated intraocular pressure, and currently lacks effective neuroprotective therapies. OPTN(E50K) mutation, a pathogenic gene of NTG, compromises paracrine trophic capacity in bone marrow (BM) stem cells. Allogeneic young BM stem cells can provide trophic support and exhibit therapeutic potential; however, their clinical application is limited by immunogenic rejection and tumorigenic risks, prompting a renewed interest in rejuvenate autologous BM stem cells strategy.
methodsTo address these challenges, we developed a composite chitosan-rapamycin (RAPA) carbon dots (CRCD) to restore the reparative potential of autologous BM stem cells. BM stem cells from aged OPTN(E50K) mice were isolated, clustered and treated with CRCD before validated their changes of neurotrophic factors expression as well as oxidative stress and autophagy indicators. Then we assessed their impact on co-cultured retinas in vitro. Transplantation were performed into lethally irradiated age-matched OPTN(E50K) hosts with CRCD-pretreated autologous BM stem cells via tail vein injection, and generated stable chimeric models. Neurotrophic factors and neuron apoptosis analyses were performed, followed by the visual behavioral tests.
resultsOur results demonstrated that CRCD pretreatment enhanced autophagy, reduced oxidative stress, and augmented paracrine neurotrophic release. In vitro, these cells reduced retinal ganglion cell apoptosis and promoted neurotrophic factor expression in co-cultured retinal explants. In vivo, comparative analysis revealed that CRCD intervention significantly elevated neurotrophic factor expression in retinal tissues compared to RAPA-treated and untreated chimeras. Functional assessments further confirmed superior visual performance in CRCD-Sca-1
conclusionThese findings suggest that CRCD improved paracrine neurotrophic support of autologous BM stem cells by enhancing their autophagy and paracrine functions, leading to structural and functional rescue of the glaucomatous retina. This approach offered a clinically relevant strategy for NTG, providing sustained neuroprotection while avoiding the risks of allogeneic transplantation and repeated intravitreal drug delivery.
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