Background/Aims: The treatment options for diabetic retinopathy (DR) are limited. Mesenchymal stem cells (MSCs) are a promising treatment option for diabetes and its complications. In this pilot clinical trial, we evaluated the safety and efficacy of intravenous autologous bone marrow MSCs (ABMSC) for the treatment of DR. Methods: In total, 34 eyes with non-proliferative or proliferative DR (NPDR, n = 19; PDR, n = 15) from 17 patients were analyzed. Treatment involved one intravenous infusion of 3 × 10⁶/kg ABSMCs. The patients’ vital signs were monitored, along with immune and allergic reactions. Treatment efficacy was evaluated via measurements of the following parameters at baseline, and at 1, 3, and 6 months after treatment: the levels of fasting blood glucose (FBG), Hemoglobin A1C (HbA_1C), interleukin-6 (IL-6), and hypersensitive C-reactive protein (CRP); best corrected visual acuity (BCVA); and central macular and subfield thickness (via optical computed tomography). Results: ABMSC infusion led to a significant decrease in FBG and CRP levels (P < 0.05). There were no significant differences in HbA_1C or IL-6 levels. Sub-group analysis revealed that only eyes in the NPDR group had the macular thickness reductions and a significant improvement in BCVA from baseline (P = 0.006 at 3 months and 0.027 at 6 months), while those in the PDR group did not. There were no acute reactions during the treatment or severe adverse events during the follow-up period. Conclusion: ABSMCs are a potentially safe and effective treatment option for DR, and the optimum therapeutic window appears to be during the NPDR stage.

It aims to explore the toxicity and mechanism of large-surface-area MSiNPs and MSiNPs-Ag⁺ exposed to hCEC cells and cornea. A protein corona-based therapy was proposed to treat MSiNPs and MSiNPs-Ag⁺ induced corneal damage and dry eye.

Diabetic retinopathy (DR), one of the leading causes of vision loss worldwide, is characterized by neurovascular disorders. Emerging evidence has demonstrated retinal neurodegeneration in the early pathogenesis of DR, and no treatment has been developed to prevent the early neurodegenerative changes that precede detectable microvascular disorders. Bone marrow CD133+ stem cells with revascularization properties exhibit neuroregenerative potential. However, whether CD133+ cells can ameliorate the neurodegeneration at the early stage of DR remains unclear. In this study, mouse bone marrow CD133+ stem cells were immunomagnetically isolated and analyzed for the phenotypic characteristics, capacity for neural differentiation, and gene expression of neurotrophic factors. After being labeled with enhanced green fluorescent protein, CD133+ cells were intravitreally transplanted into streptozotocin (STZ)-induced diabetic mice to assess the outcomes of visual function and retina structure and the mechanism underlying the therapeutic effect. We found that CD133+ cells co-expressed typical hematopoietic/endothelial stem/progenitor phenotypes, could differentiate to neural lineage cells, and expressed genes of robust neurotrophic factors in vitro. Functional analysis demonstrated that the transplantation of CD133+ cells prevented visual dysfunction for 56 days. Histological analysis confirmed such a functional improvement and showed that transplanted CD133+ cells survived, migrated into the inner retina (IR) over time and preserved IR degeneration, including retina ganglion cells (RGCs) and rod-on bipolar cells. In addition, a subset of transplanted CD133+ cells in the ganglion cell layer differentiated to express RGC markers in STZ-induced diabetic retina. Moreover, transplanted CD133+ cells expressed brain-derived neurotrophic factors (BDNFs) in vivo and increased the BDNF level in STZ-induced diabetic retina to support the survival of retinal cells. Based on these findings, we suggest that transplantation of bone marrow CD133+ stem cells represents a novel approach to ameliorate visual dysfunction and the underlying IR neurodegeneration at the early stage of DR.

Retinitis pigmentosa initially presents as night blindness owing to defects in rods, and the secondary degeneration of cones ultimately leads to blindness. Previous studies have identified active roles of microglia in the pathogenesis of photoreceptor degeneration in RP. However, the contribution of microglia to photoreceptor degeneration remains controversial, partly due to limited knowledge of microglial phenotypes during RP. Rationale: In this study, we investigated the pathways of microglial activation and its contribution to photoreceptor degeneration in RP. Methods: A classic RP model, Royal College of Surgeons rat, was used to explore the process of microglial activation during the development of RP. An inhibitor of colony-stimulating factor 1 receptor (PLX3397) was fed to RCS rats for sustained ablation of microglia. Immunohistochemistry, flow cytometry, RT-qPCR, electroretinography and RNA-Seq were used to investigate the mechanisms by which activated microglia influenced photoreceptor degeneration. Results: Microglia were gradually activated to disease-associated microglia in the photoreceptor layers of RCS rats. Sustained treatment with PLX3397 ablated most of the disease-associated microglia and aggravated photoreceptor degeneration, including the secondary degeneration of cones, by downregulating the expression of genes associated with photoreceptor function and components and exacerbating the impairment of photoreceptor cell function. Disease-associated microglial activation promoted microglia to engulf apoptotic photoreceptor cell debris and suppressed the increase of infiltrated neutrophils by increasing engulfment and inhibiting CXCL1 secretion by Müller cells, which provided a healthier microenvironment for photoreceptor survival. Conclusions: Our data highlight a key role of disease-associated microglia activation in the suppression of rod and cone degeneration, which reduces secondary damage caused by the accumulation of dead cells and infiltrated neutrophils in the degenerating retina.