Mesenchymal stem cells (MSCs) represent the promising options for retinal therapy and combined therapy with nanoparticles (NPs) could currently provide increased immunoregulatory and neuroprotective effects. Therefore, we tested the effect of silver (Ag)NPs on the properties of MSCs in an experimental model of chronic retinal degeneration. The results showed that simultaneous administration had no effect on the survival of MSCs, but a less effective local regulation of Iba-1 expression compared to MSC- or AgNP-only treated groups was observed. In addition, MSCs applied alone or in combination with AgNPs and sorted from the degenerated retina had increased expression of genes for retinal markers (rhodopsin, S-antigen, recoverin), and for TGF-β and IGF-1. These effects were confirmed also on protein level by increased production of IGF-1 and proportion of rhodopsin+ MSCs. Nevertheless, the increased expression of the gene for GDNF was observed only in the MSCs combined with AgNPs. Regarding the immune response, the application of MSCs with AgNPs triggered increased expression of the IL-6 gene in the CD45 cells separated from the retina. In conclusion, applications of MSCs or AgNPs, as a single therapy, were able to modulate the inflammation. However, the combined applications decreased the immunomodulatory effects of MSCs or AgNPs.

• Keywords
• Mesenchymal stem cells, Retina, Retinal microglia, Silver nanoparticles,
• MeSH
• Retinal Degeneration * therapy   chemically induced   pathology   MeSH
• Iodates toxicity   MeSH
• Combined Modality Therapy MeSH
• Metal Nanoparticles * chemistry   administration & dosage   MeSH
• Mesenchymal Stem Cells * metabolism   cytology   drug effects   MeSH
• Disease Models, Animal MeSH
• Mice MeSH
• Retina metabolism   pathology   MeSH
• Silver * chemistry   pharmacology   MeSH
• Mesenchymal Stem Cell Transplantation * methods   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH
• Names of Substances
• Iodates MeSH
• sodium iodate MeSH Browser
• Silver * MeSH

Activation of immune response plays an important role in the development of retinal diseases. One of the main populations of immune cells contributing to the retinal homeostasis are microglia, which represent a population of residential macrophages. However, under pathological conditions, microglia become activated and rather support a harmful inflammatory reaction and retinal angiogenesis. Therefore, targeting these cells could provide protection against retinal neuroinflammation and neovascularization. In the recent study, we analyzed effects of silver nanoparticles (AgNPs) on microglia in vitro and in vivo. We showed that the AgNPs interact in vitro with stimulated mouse CD45/CD11b positive cells (microglia/macrophages), decrease their secretion of nitric oxide and vascular endothelial growth factor, and regulate the expression of genes for Iba-1 and interleukin-1β (IL-1β). In our in vivo experimental mouse model, the intravitreal application of a mixture of proinflammatory cytokines tumor necrosis factor-α, IL-1β and interferon-γ induced local inflammation and increased local expression of genes for inducible nitric oxide synthase, IL-α, IL-1β and galectin-3 in the retina. This stimulation of local inflammatory reaction was significantly inhibited by intravitreal administration of AgNPs. The application of AgNPs also decreased the presence of CD11b/Galectin-3 positive cells in neuroinflammatory retina, but did not influence viability of cells and expression of gene for rhodopsin in the retinal tissue. These data indicate that AgNPs regulate reactivity of activated microglia in the diseased retina and thus could provide a beneficial effect for the treatment of several retinal diseases.

• Keywords
• Microglia, Neovascularization, Neuroinflammation, Retinal diseases, Silver nanoparticles,
• MeSH
• Metal Nanoparticles * administration & dosage   MeSH
• Macrophages drug effects   immunology   MeSH
• Microglia drug effects   immunology   metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Retina * drug effects   immunology   pathology   MeSH
• Silver * pharmacology   administration & dosage   therapeutic use   MeSH
• Inflammation drug therapy   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Silver * MeSH

The eye represents a highly specialized organ, with its main function being to convert light signals into electrical impulses. Any damage or disease of the eye induces a local inflammatory reaction that could be harmful for the specialized ocular cells. Therefore, the eye developed several immunoregulatory mechanisms which protect the ocular structures against deleterious immune reactions. This protection is ensured by the production of a variety of immunosuppressive molecules, which create the immune privilege of the eye. In addition, ocular cells are potent producers of numerous growth and trophic factors which support the survival and regeneration of diseased and damaged cells. If the immune privilege of the eye is interrupted and the regulatory mechanisms are not sufficiently effective, the eye disease can progress and result in worsening of vision or even blindness. In such cases, external immunotherapeutic interventions are needed. One perspective possibility of treatment is represented by mesenchymal stromal/stem cell (MSC) therapy. MSCs, which can be administered intraocularly or locally into diseased site, are potent producers of various immunoregulatory and regenerative molecules. The main advantages of MSC therapy include the safety of the treatment, the possibility to use autologous (patient's own) cells, and observations that the therapeutic properties of MSCs can be intentionally regulated by external factors during their preparation. In this review, we provide a survey of the immunoregulatory and regenerative mechanisms in the eye and describe the therapeutic potential of MSC application for corneal damages and retinal diseases.

• Keywords
• cell therapy, corneal damages, immunoregulation, mesenchymal stem cells, retinal diseases, tissue regeneration,
• MeSH
• Humans MeSH
• Mesenchymal Stem Cells * cytology   MeSH
• Retinal Diseases * therapy   immunology   MeSH
• Corneal Injuries * therapy   MeSH
• Mesenchymal Stem Cell Transplantation * methods   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The retina represents a highly specialized structure with the primary function to capture a light signal and to convert it into electrical impulses. Any damage or disease of the retina can cause visual impairment. Since retinal degenerative diseases are generally associated with immune cell infiltration, a local inflammatory reaction, and cytokine burn, there is a need for mechanisms to prevent the retina from damage by a deleterious immune reaction. In this study, we show that mouse retinal explants co-cultivated with stimulated spleen cells, inhibit in a dose-dependent manner the activation of T cells, and suppress the production of cytokines interleukin-2, interleukin-10, and interferon-[Formula: see text]. The immunoregulatory properties of the retina were mainly mediated by a paracrine effect since retinal explants, separated by a semipermeable membrane, or supernatants obtained after the cultivation of retinal explants, inhibited the reactivity of immune cells. A model of retinal damage was established by the application of sodium iodate which selectively destroys photoreceptors, as it was demonstrated by a decrease in the number of rhodopsin-positive cells. This process was accompanied by increased infiltration of the retina with cells of the immune system and by a local inflammatory reaction. The pharmacologically damaged retina had significantly decreased the ability to inhibit T cell activation and production of cytokines by immune cells. Overall, the results showed that the retina possesses immunoregulatory properties and inhibits the activation and functions of T cells. However, the immunomodulatory properties of the retina are decreased if the retina is damaged.

• Keywords
• cytokines, healthy retina, immunosuppression, inflammatory eye, pharmacologically damaged retina,
• MeSH
• Cytokines * metabolism   MeSH
• Mice MeSH
• Retina * MeSH
• Inflammation metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Cytokines * MeSH

Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy or glaucoma, represent the main causes of a decreased quality of vision or even blindness worldwide. However, despite considerable efforts, the treatment possibilities for these disorders remain very limited. A perspective is offered by cell therapy using mesenchymal stem cells (MSCs). These cells can be obtained from the bone marrow or adipose tissue of a particular patient, expanded in vitro and used as the autologous cells. MSCs possess potent immunoregulatory properties and can inhibit a harmful inflammatory reaction in the diseased retina. By the production of numerous growth and neurotrophic factors, they support the survival and growth of retinal cells. In addition, MSCs can protect retinal cells by antiapoptotic properties and could contribute to the regeneration of the diseased retina by their ability to differentiate into various cell types, including the cells of the retina. All of these properties indicate the potential of MSCs for the therapy of diseased retinas. This view is supported by the recent results of numerous experimental studies in different preclinical models. Here we provide an overview of the therapeutic properties of MSCs, and their use in experimental models of retinal diseases and in clinical trials.

• Keywords
• clinical trials, experimental models, mesenchymal stem cells, retinal degenerative diseases, stem cell therapy,
• MeSH
• Transplantation, Autologous MeSH
• Cell- and Tissue-Based Therapy methods   MeSH
• Cell Differentiation MeSH
• Bone Marrow Cells cytology   metabolism   MeSH
• Diabetic Retinopathy genetics   metabolism   pathology   therapy   MeSH
• Glaucoma genetics   metabolism   pathology   therapy   MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Macular Degeneration genetics   metabolism   pathology   therapy   MeSH
• Mesenchymal Stem Cells cytology   metabolism   MeSH
• Intercellular Signaling Peptides and Proteins genetics   metabolism   MeSH
• Disease Models, Animal MeSH
• Nerve Growth Factors genetics   metabolism   MeSH
• Retina metabolism   pathology   MeSH
• Retinitis Pigmentosa genetics   metabolism   pathology   therapy   MeSH
• Mesenchymal Stem Cell Transplantation methods   MeSH
• Adipose Tissue cytology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• Intercellular Signaling Peptides and Proteins MeSH
• Nerve Growth Factors MeSH