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Background: Polarization of microglia, the resident retinal immune cells, plays important roles in mediating both injury and repair responses post-retinal ischemia–reperfusion (I/R) injury, which is one of the main pathological mechanisms behind ganglion cell apoptosis. Aging could perturb microglial balances, resulting in lowered post-I/R retinal repair. Young bone marrow (BM) stem cell antigen 1-positive (Sca-1+) cells have been demonstrated to have higher reparative capabilities post-I/R retinal injury when transplanted into old mice, where they were able to home and differentiate into retinal microglia. Methods: Exosomes were enriched from young Sca-1+ or Sca-1− cells, and injected into the vitreous humor of old mice post-retinal I/R. Bioinformatics analyses, including miRNA sequencing, was used to analyze exosome contents, which was confirmed by RT-qPCR. Western blot was then performed to examine expression levels of inflammatory factors and underlying signaling pathway proteins, while immunofluorescence staining was used to examine the extent of pro-inflammatory M1 microglial polarization. Fluoro-Gold labelling was then utilized to identify viable ganglion cells, while H&E staining was used to examine retinal morphology post-I/R and exosome treatment. Results: Sca-1+ exosome-injected mice yielded better visual functional preservation and lowered inflammatory factors, compared to Sca-1−, at days 1, 3, and 7 days post-I/R. miRNA sequencing found that Sca-1+ exosomes had higher miR-150-5p levels, compared to Sca-1− exosomes, which was confirmed by RT-qPCR. Mechanistic analysis found that miR-150-5p from Sca-1+ exosomes repressed the mitogen-activated protein kinase kinase kinase 3 (MEKK3)/JNK/c-Jun axis, leading to IL-6 and TNF-α downregulation, and subsequently reduced microglial polarization, all of which contributes to reduced ganglion cell apoptosis and preservation of proper retinal morphology. Conclusion: This study elucidates a potential new therapeutic approach for neuroprotection against I/R injury, via delivering miR-150-5p-enriched Sca-1+ exosomes, which targets the miR-150-5p/MEKK3/JNK/c-Jun axis, thereby serving as a cell-free remedy for treating retinal I/R injury and preserving visual functioning. [ABSTRACT FROM AUTHOR]

Ischemic cardiac injury is the main contributor to heart failure, and the regenerative capacity of intrinsic stem cells plays an important role in tissue repair after injury. However, stem cells in aged individuals have reduced regenerative potential and aged tissues lack the capacity to renew. Growth differentiation factor 11 (GDF11), from the activin-transforming growth factor β superfamily, has been shown to promote stem cell activity and rejuvenation. We carried out non-invasive targeted delivery of the GDF11 gene to the heart using ultrasound-targeted microbubble destruction (UTMD) and cationic microbubble (CMB) to investigate the ability of GDF11 to rejuvenate the aged heart and improve tissue regeneration after injury. Young (3 months) and old (21 months) mice were used to evaluate the expression of GDF11 mRNA in the myocardium at baseline and after ischemia/reperfusion (I/R) and myocardial infarction. GDF11 expression decreased with age and following myocardial injury. UTMD-mediated delivery of the GDF11 plasmid to the aged heart after I/R injury effectively and selectively increased GDF11 expression in the heart, and improved cardiac function and reduced infarct size. Over-expression of GDF11 decreased senescence markers, p16 and p53, as well as the number of p16 + cells in old mouse hearts. Furthermore, increased proliferation of cardiac stem cell antigen 1 (Sca-1 + ) cells and increased homing of endothelial progenitor cells and angiogenesis in old ischemic hearts occurred after GDF11 over-expression. Repetitive targeted delivery of the GDF11 gene via UTMD can rejuvenate the aged mouse heart and protect it from I/R injury.

Objective: To investigate the role of connective tissue growth factor (CTGF) after trabeculectomy associated with wound healing and to identify the role of CTGF in this process., Methods: It was a experimental study. Forty-nine rabbits were used and divided into 5 groups: normal eyes without trabeculectomy group (group A), ocular hypertension (OHT) model without trabeculectomy group (group B), OHT model with trabeculectomy group (group C), normal eyes with trabeculectomy group (group D) and normal eyes with sham operation group (group E). Group A and B were as control. CTGF mRNA was detected by RT-PCR using blebs and tissues harvested at day 2, 5, 7, and 14. Three replicates of three blebs per time point in the right eyes were collected. The expression of CTGF protein was detected by immunohistochemistry and inflammatory histopathology was inspected by HE staining using the whole eyeball harvested in the left eyes., Results: Compared to group A and B, the expression of CTGF was significantly increased at day 5 after surgery (F = 19.54, P < 0.05) in group C, D, and E. The expression of CTGF mRNA in group C is significantly higher than that in group D at day 2 and 5 (t = 2.300, 5.140, P < 0.05), while group D is significantly higher than that in group E at day 2, 5, 7, and 14 (t = -2.927, -6.424, -4.176, -4.997, P < 0.05). The expression of CTGF protein in group C is significantly higher than that in group D (t = -7.147, -10.955, -9.900, -6.385, P < 0.05), and group D is higher than that in group E (F = 68.33, P < 0.05) at day 2, 5, 7, and 14, respectively. Inflammatory reaction reached peak at day 5 after surgery in group C, D, and E showing an infiltration of neutrophil, monocytes, macrophages, and the proliferation of fibroblast., Conclusions: Overexpression of CTGF in the blebs after trabeculectomy demonstrates that CTGF may play an important role in the process of wound healing. Furthermore, ocular hypertension may be involved in the upregulation of CTGF expression.

Objective: To investigate the prevalence of primary angle-closure glaucoma (PACG) and its causes in a rural area in Changchun, China., Methods: From the rural area of Qijiaxiang, Shuangyang district of Changchun, 1139 individuals aged 40 years and above were randomly selected for the study from September 2004 to February 2005 using Zhao Jialiang's standard. All subjects in this study underwent a preliminary screening examination including visual acuity, the peripheral depth of anterior chamber, slit lamp, tonometry and fundus. The suspects of PACG were asked to repeat the following examinations: tonometry, gonioscopy, fundus, and visual field assessment., Results: 1139 of 1528 subjects were invited to participate in the study (response rate 74.5%). In those age 40 years and above, the prevalence of PACG was 1.5% in men, 3.5% in women, and 2.5% in general population, respectively. The prevalence was increased with age. The anterior chamber was significantly (P<0.01) narrower in the female group than in the male group when the peripheral depth of anterior chamber was compared. The prevalence of PACG was significantly (P<0.02) higher in subjects with positive family history than with negative family history., Conclusions: In the rural area in Shuangyang district of Changchun, the prevalence of PACG is higher than other regions surveyed in China. Sex, age, family history and the peripheral depth of anterior chamber are significant risk factors in PACG.