Exosomal miR-181d-5p Derived from Rapamycin-Conditioned MDSC Alleviated Allograft Rejection by Targeting KLF6.

Immune rejection and side effects of long-term administration of immunosuppressants are the two major obstacles to allograft acceptance and tolerance. The immunosuppressive extracellular vesicles (EVs)-based approach has been proven to be effective in treating autoimmune/inflammatory disorders. Herein, the anti-rejection advantage of exosomes (Rapa-Exo) from rapamycin-conditioned myeloid-derived suppressor cells (MDSCs) over exosomes (Exo-Nor) from the untreated MDSCs is shown. The exosomal small RNA sequencing and loss-of-function assays reveal that the anti-rejection effect of Rapa-Exo functionally relies on miR-181d-5p. Through target prediction and double-luciferase reporter assay, Kruppel-like factor (KLF) 6 is identified as a direct target of miR-181d-5p. Finally, KLF6 knockdown markedly resolves inflammation and prolongs the survival of corneal allografts. Taken together, these findings support that Rapa-Exo executes an anti-rejection effect, highlighting the immunosuppressive EVs-based treatment as a promising approach in organ transplantation.

Clinical Characteristics and Outcomes of Short-term Repeat Corneal Transplantation.

PURPOSE: To explore the primary indications, direct causes and graft survival of short-term repeat keratoplasty. METHODS: An analytical cross-sectional study. RESULTS: The primary indications for keratoplasty were infectious keratitis (67.9%) and immune keratopathy (12.8%). The direct causes of graft failure were infectious ulcer (43.6%) and recurrence (30.8%). Pre-operative hypopyon (P = 0.017, HR = 1.757) and use of decellularized porcine corneas as grafts (P = 0.005, HR = 2.690) were independent risk factors for graft failure. The Kaplan-Meier analysis revealed that the 1-year survival rate of 88 repeat grafts was 85.2%, and the 5-year survival rate was 79.2%. The survival rates of the repeat grafts were significantly higher than those of the first grafts (P < 0.001). CONCLUSION: Infectious keratitis is the most common indication of short-term graft failure and is often failed by infectious ulcer and keratitis recurrence. While the decellularized porcine cornea is a promising application in developing countries, certain difficulties, such as graft melting, remain unresolved.

Comparison of complications and visual outcomes between big-bubble deep anterior lamellar keratoplasty and penetrating keratoplasty for fungal keratitis.

BACKGROUND: To compare the postoperative complications and visual outcomes of big-bubble deep anterior lamellar keratoplasty (BB-DALK) and penetrating keratoplasty (PK) for fungal keratitis (FK). METHODS: This retrospective study included 94 cases of BB-DALK for FK and 161 cases of PK for FK from a tertiary ophthalmology care centre. RESULTS: The most common FK pathogens were Fusarium (n = 84, 32.9%) and Aspergillus (n = 67, 26.3%). The recurrence rates after BB-DALK and PK were 3.2 and 5%, respectively (p = 0.723). The follow-up duration was 31.9 ± 15.8 months in the BB-DALK group and 33.9 ± 15.0 months in the PK group. The immune rejection rate was significantly lower in the BB-DALK group than in the PK group (1.1 vs. 18.6%, p < 0.001), as was the incidence of secondary glaucoma (p = 0.018). Endothelial cell density in the BB-DALK group tended to be stable at postoperative month 6, whereas the PK group still attenuated at a hyper-physiological rate. Postoperative best-corrected visual acuity (BCVA) significantly improved in both groups (p < 0.001). No significant difference between-group was observed in BCVA, refractive cylinder, and spherical equivalent postoperatively. CONCLUSION: Big-bubble DALK is a useful and safe alternative to PK for medically uncontrolled FK.

Deep Eutectic Solvents as Active Pharmaceutical Ingredient Delivery Systems in the Treatment of Metabolic Related Diseases.

Metabolic related diseases such as cancer, diabetes mellitus and atherosclerosis are major challenges for human health and safety worldwide due to their associations with high morbidity and mortality. It is of great significance to develop the effective active pharmaceutical ingredient (API) delivery systems for treatment of metabolic diseases. With their unique merits like easy preparation, high adjustability, low toxicity, low cost, satisfactory stability and biodegradation, deep eutectic solvents (DESs) are unarguably green and sustainable API delivery systems that have been developed to improve drug solubility and treat metabolic related diseases including cancer, diabetes mellitus and atherosclerosis. Many reports about DESs as API delivery systems in the therapy of cancer, diabetes mellitus and atherosclerosis exist but no systematic overview of these results is available, which motivated the current work.

Multi-level consistent changes of the ECM pathway identified in a typical keratoconus twin's family by multi-omics analysis.

BACKGROUND: Keratoconus (KC) is a common, degenerative disorder of the cornea, and genetic factors play a key role in its development. However, the genetic etiology of KC is still unclear. This study used the family of twins as material, using, for the first time, multi-omics analysis, to systematically display the changes in KC candidate factors in patients at the DNA, RNA, and protein levels. These can evaluate candidate pathogenic factors in depth and lock onto pathogenic targets. RESULTS: The twins in this study presented classic phenotypes, clear diagnoses, complete case data, and clinical samples, which are excellent materials for genetically studying KC. Whole-exome sequencing was conducted on both the twins and their parents. Transcriptome sequencing was conducted on proband's and health individual's primary human corneal fibroblast cells. Quantitative Real-time PCR and western blot were used to validate the differential gene expressions between the proband and controls. By integrating genomics, transcriptome, and protein level data, multiple consecutive events of KC were systematically analyzed to help better understand the molecular mechanism and genetic basis of KC. The results showed that the accumulation of rare, micro-effect risk variants was the pathogenic factor in this Chinese KC family. Consistent changes in extracellular matrices (ECMs) at the DNA and RNA levels suggested that ECM related changes play a key role in KC pathogenesis. The major gene variants (WNT16, CD248, COL6A2, COL4A3 and ADAMTS3) may affect the expression of related collagens or ECM proteins, thus reducing the amount of ECM in corneas and resulting in KC. CONCLUSIONS: This study, the first to explore the genetic etiology of KC via multi-omics analysis under the polygenetic model, has provided new insights into the genetic mechanisms underlying KC and an effective strategy for studying KC pathogenesis in the future.

Clinical Characteristics and Visual Outcomes of Patients Hospitalized for Ocular Trauma in Shandong Province, China.

PURPOSE: To analyze the clinical characteristics and visual prognoses of patients with ocular trauma treated in Shandong Eye Hospital. METHODS: The inpatient data of patients with eye injuries hospitalized in our institution from January 2014 to December 2018 were retrospectively reviewed, including demographic information, types of trauma, causes of injury, treatment, and initial and final visual acuities. RESULTS: A total of 1,425 patients (1,622 eyes), aged 39.5 ± 18.5 years, were included. The ratio of male to female was 5.3 : 1. Of the mechanical eye injuries, there were 490 (34.4%) open-globe injuries and 454 (31.9%) closed-globe injuries. Nonmechanical eye injuries had 426 patients (29.9%), while 55 patients (3.9%) had adnexal injuries. Over a half of the traumas were work-related (51.1%, 728 patients). Most patients were treated with surgical intervention (1,404 eyes, 87.9%). There were significant differences in the final visual acuities between open-globe injuries and closed-globe injuries (P < 0.001), as well as between mechanical injuries and nonmechanical injuries (P < 0.001). The final visual acuity was closely correlated with the initial visual acuity (Spearman's correlation coefficient = 0.618, P < 0.001) and the OTS score (Spearman's correlation coefficient = 0.691, P < 0.001). CONCLUSION: Ocular trauma usually occurs in young and middle-aged men and in the workplace in Shandong Province. The proportion of nonmechanical injuries is high, and the prognosis is poor. A comprehensive understanding of the characteristics of ocular trauma is useful for blindness prevention and treatment.