Mesenchymal Stem Cell Transplantation in Type 1 Diabetes Treatment: Current Advances and Future Opportunity.

Type 1 Diabetes (T1D) is characterized by hyperglycemia, and caused by a lack of insulin secretion. At present there is no cure for T1D and patients are dependent on exogenous insulin for lifelong, which seriously affects their lives. Mesenchymal stem cells (MSCs) can be differentiated to ß cell-like cells to rescue the secretion of insulin and reconstruct immunotolerance to preserve the function of islet ß cells. Due to the higher proportion of children and adolescents in T1D patients, the efficacy and safety issue of the application of MSC's transplant in T1D was primarily demonstrated and identified by human clinical trials in this review. Then we clarified the mechanism of MSCs to relieve the symptom of T1D and found out that UC-MSCs have no obvious advantage over the other types of MSCs, the autologous MSCs from BM or menstrual blood with less expanded ex vivo could be the better choice for clinical application to treat with T1D through documentary analysis. Finally, we summarized the advances of MSCs with different interventions such as genetic engineering in the treatment of T1D, and demonstrated the advantages and shortage of MSCs intervened by different treatments in the transplantation, which may enhance the clinical efficacy and overcome the shortcomings in the application of MSCs to T1D in future.

Mechanisms of NO-Mediated Protein S-Nitrosylation in the Lens-Induced Myopia.

Background: Myopia is a chronic ocular disease, emerging as the most common type of refractive error. This study intends to preliminarily explore the roles of protein S-nitrosylation of nitric oxide (NO) in the regulation of myopia by detecting the expression of neuronal nitric oxide synthase (nNOS) and downstream S-nitrosylation, using the animal model of lens-induced myopia (LIM) in mice. Methods: The 3-week-old C57BL/6 J mice were divided into three groups: group I, lens-induced 0-week group (take eyeballs at the age of 3 weeks); group II, self-control eyes of experimental group (take eyeballs at the age of 7 weeks); and group III, lens-induced 4-week group (take eyeballs at the age of 7 weeks). The diopter and axial length of each group were measured by streak retinoscopes and optical coherence tomography (OCT) before and after model establishment. The protein expressions and locations of nNOS and S-nitrosylated proteins (PSNOs) were measured by western blot and immunofluorescence staining. Site-specific proteomic for protein S-nitrolysation was used to detect the existence and location of S-nitrosylation proteins in the retina of myopic and nonmyopic mice. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and motif enrichment analyses were performed. The differential sites were analyzed by GO, KEGG, and motif. Irreversible biotinylation procedure combined with protein purification and western blot was used to detect the protein expression of α-enolase (ENO1), a key player in the hypoxia-related signal pathway. Results: The expressions of nNOS and PSNOs were significantly lower in the retina of experimental eyes than that in self-control eyes and 3-week-old baseline group. A total of 595 S-nitrosylated proteins, 709 S-nitrosylated peptides, and 708 S-nitrosylated sites were identified by site-specific S-nitrolysation proteomics in the retina of myopic and control eyes. A total of 19 differentiation loci were screened, of which 13 sites were downregulated and 6 sites were upregulated in experimental eyes compared with the self-control group. Specifically, the expression of SNO-ENO1 was significantly lower in the retina of experimental eyes than that in self-control eyes and 3-week-old baseline group. Conclusion: LIM induces the decrease of nNOS and PSNO protein levels in the retina of myopic mice. NO-mediated nonclassical protein S-nitrosylation modification may play an important role in the regulation of lens-induced myopia. ENO1 may be a key factor in the regulation of S-nitrosylation modification of myopia.

Age of Rats Affects the Degree of Retinal Neuroinflammatory Response Induced by High Acute Intraocular Pressure.

PURPOSE: To investigate whether retinal neuroinflammatory response was affected by aging in a rat model of acute glaucoma. METHODS: Young adult and aged rats were randomly assigned into normal control, 45 mmHg, 60 mmHg, and 90 mmHg groups. Intraocular pressure (IOP) of rats was acutely elevated to 45 mmHg, 60 mmHg, and 90 mmHg, respectively. Three days after high IOP treatment, loss of retinal ganglion cells (RGCs), formation of proinflammatory microglia/macrophages and neurotoxic astrocytes, and deposition of complement C3 in the retina were detected by immunofluorescence. ELISA was used to assess the protein levels of proinflammatory cytokines TNF and IL-1ß in the retina. RESULTS: Compared with young adult retinae, (1) loss of RGCs was more severe in aged retinae under the same IOP treatment, (2) microglia/macrophages were more prone to adopt proinflammatory phenotype in aged retinae in response to elevated IOP, (3) high IOP treatment induced astrogliosis, formation of neurotoxic astrocytes, and deposition of complement C3 more easily in aged retinae, and (4) aged retinae induced higher levels of proinflammatory cytokines TNF and IL-1ß under the same IOP treatment. CONCLUSION: Our data indicated that aging affects the degree of retinal neuroinflammatory response initiated by ocular hypertension, which may contribute to the age-related susceptibility of RGCs to elevated IOP.