Purpose: To explore the microRNA (miRNA) profile and its putative role in glaucomatous optic neuropathy by using next-generation sequencing. Methods: Aqueous humor (AH) samples were collected from 19 primary open-angle glaucoma (POAG) eyes and 17 cataract eyes before surgery. Next-generation sequencing was performed for RNA samples extracted from 18 AH samples, and the bioinformatics approach was applied for samples with adequate clean data output. The other 18 samples were used for quantitative PCR validation of sequencing results. Results: In total, 12 (six POAG and six cataract controls) samples with sufficient clean data output after sequencing were used for further data analysis. Four hundred sixty-six and 480 mature miRNAs were detected in the POAG and cataract control groups, respectively. Among them, 164 miRNAs were detected in all POAG samples, and 96 miRNAs were detected in all cataract control samples. Furthermore, 88 miRNAs were identified as differently expressed between POAG and cataract control eyes. In addition, 16 miRNAs were differently expressed between POAG eyes with severe visual field damage and eyes with moderate visual field damage. This differential expression was predicted to regulate thiamine metabolism, purine metabolism, and transcriptional misregulation. Relative expression patterns of hsa-miR-184, hsa-miR-486-5p, and hsa-miR-93-5p were confirmed by quantitative PCR. Conclusions: This study comprehensively demonstrated the miRNA expression profile in the AH of POAG eyes, especially the differential expression of miRNA in eyes with varying degrees of visual field damage, which, together with the underlying miRNA-related pathways, indicate new targets for the pathogenesis and progression of POAG.

Glaucoma is a common neurodegenerative disease and a leading cause of irreversible blindness worldwide. Retinal microglia-mediated neuroinflammation is involved in the process of optic nerve damage, but the mechanisms driving this microglial activation remain mostly elusive. Previous investigations reported that microRNAs are associated with the retinal microglial reaction and neural apoptosis. In the present study, we found that microRNA-93-5p (miR-93) played a key role in the reaction of retinal microglial cells in vivo and in vitro. The miR-93 level was significantly reduced in the retinae of rat acute ocular hypertension (AOH) models, which were accompanied by retinal microglial activation, overproduction of inflammatory cytokines, and subsequent retinal ganglion cells (RGCs) death, versus the retinae of controls. The induction of miR-93 overexpression significantly reduced microglial proliferation, migration and cytokine release, inhibited the expression of the target gene signal transducer and activator of transcription 3 (STAT3) and p-STAT3, and was associated with a reduced loss of RGCs. Treatment with a STAT3 inhibitor also decreased retinal microglial activation after AOH injury. Taken together, these results suggest that the miR-93/STAT3 pathway is directly related to the downregulation of retinal microglia-mediated neuro-inflammation and showed a neuroprotective effect. Regulating microglial activation through miR-93 may serve as a target for neuroprotective therapy in pathological ocular hypertension.

Acute primary angle-closure (APAC) eyes show an early ‘acute inflammatory’ condition, while the inflammation condition has not been fully elucidated in the development of primary angle-closure glaucoma (PACG). To evaluate the roles of inflammatory cytokines in the pathogenesis of PACG, this cross-sectional study involved 40 eyes of 32 PACG patients who required trabeculectomy and 24 eyes of 24 patients who required cataract surgery. The aqueous humor samples were collected at the time of surgery. Fifteen inflammatory cytokines were detected using the multiplex bead immunoassay technique, and the clinical information was recorded for the correlation analysis. Eight of the 15 cytokines were all detectable in both groups, including granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, MCP-3, macrophage-derived chemokine (MDC), macrophage inflammatory protein (MIP)-1β, and vascular endothelial growth factor (VEGF). When compared with the cataract patients, the MCP-3, MDC, and VEGF levels were elevated in the PACG patients, while the MCP-1 and MIP-1β levels were decreased. However, the G-CSF, IL-6, and IL-8 levels were similar between the two groups. The MCP-1 concentration was elevated accordingly as the disease progressed in the PACG patients. Our results suggest the PACG eyes retained a ‘mild inflammation’ condition in the aqueous humor, and MCP-1 may play an important role in the progression of this disease.

Purpose: Blood-based examination tools for glaucoma diagnosis in clinical practice, which can be useful for screening patients when traditional ophthalmic examinations cannot be utilized, are not available thus far. This study aimed to identify circulating microRNAs (miRNAs) associated with primary open-angle glaucoma (POAG) and explore their utility as diagnostic markers. Methods: A total of 136 POAG patients and controls were enrolled. Next-generation RNA sequencing was used to explore the expression profile of circulating miRNAs in the sequencing set, and potential miRNAs from independent samples in both the screening and validation sets were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) analysis was used to evaluate the ability of certain miRNAs to distinguish POAG patients from control subjects. Results: Using sequencing and qRT-PCR, hsa-miR-210-3p was found to be elevated in POAG patients in all sets. ROC analysis of the screening and validation sets revealed that hsa-miR-210-3p differentiated between POAG patients and matched controls with an area under the curve (AUC) of 0.846 (sensitivity: 84.6%; specificity: 80.8%) and 0.813 (sensitivity: 84.8%; specificity: 69.7%), respectively. In case of all nonsequencing participants, analysis revealed that hsa-miR-210-3p differentiated between severe POAG patients and controls with an AUC of 0.880 (sensitivity: 85.4%; specificity: 85.7%). In addition, the expression of hsa-miR-210-3p was associated with visual field defects of |mean deviation| (β = 0.237; P = 0.022) and average retinal nerve fiber layer thickness (β = −5.792; P = 0.014). Conclusions: Circulating hsa-miR-210-3p may serve as a potential diagnostic marker for POAG (especially for severe POAG patients).

Objective: To compare the efficacy and safety of macular buckling and vitrectomy for myopic traction maculopathy showing macular schisis (MS) and associated macular detachment (MD) but without full‐thickness macular hole (FTMH).Design: Prospective, randomized, parallel, open‐label study.Methods: Patients were randomly assigned to either buckling or vitrectomy group. Macular buckling and intravitreal C3F8 gas injection were performed in the buckling group. Small gauge vitrectomy, internal limiting membrane peeling (ILMP) and C3F8 gas tamponade were performed in the vitrectomy group. The patients were followed for 12 months.Main outcome measures: Best‐corrected visual acuity (BCVA) at 12 months.Results: A total of 85 patients were randomized, 80 eyes were included (41 receiving buckling, 39 received vitrectomy), and 78 patients completed the study. There were less eyes determined as surgical failure and required a second surgery in the buckling group than vitrectomy the group (2.4% versus 18.4%, p = 0.021). After surgery, macular buckling achieved more improvement in BCVA (+21.7 versus +4.5 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, p = 0.002). FTMH development was observed in only 1 (2.4%) eye, after removing of the implant due to recurrent conjunctival erosion, in the buckling group and 10 (26.3%) eyes (seven with‐, three without MD) in the vitrectomy group (p < 0.001). More eyes developed cataracts in the vitrectomy group than did in the buckling group (28.9% versus 7.5%, p = 0.014). Macular buckling‐associated strabismus (esotropia), binocular diplopia and implant exposure were observed in limited cases.Conclusions and relevance: Macular buckling is superior to vitrectomy with ILM peeling plus gas injection for surgical treatment of MS and associated MD in high myopia.