Assessment of visual function in blind mice and monkeys with subretinally implanted nanowire arrays as artificial photoreceptors.

Retinal prostheses could restore image-forming vision in conditions of photoreceptor degeneration. However, contrast sensitivity and visual acuity are often insufficient. Here we report the performance, in mice and monkeys with induced photoreceptor degeneration, of subretinally implanted gold-nanoparticle-coated titania nanowire arrays providing a spatial resolution of 77.5 µm and a temporal resolution of 3.92 Hz in ex vivo retinas (as determined by patch-clamp recording of retinal ganglion cells). In blind mice, the arrays allowed for the detection of drifting gratings and flashing objects at light-intensity thresholds of 15.70-18.09 µW mm-2, and offered visual acuities of 0.3-0.4 cycles per degree, as determined by recordings of visually evoked potentials and optomotor-response tests. In monkeys, the arrays were stable for 54 weeks, allowed for the detection of a 10-µW mm-2 beam of light (0.5° in beam angle) in visually guided saccade experiments, and induced plastic changes in the primary visual cortex, as indicated by long-term in vivo calcium imaging. Nanomaterials as artificial photoreceptors may ameliorate visual deficits in patients with photoreceptor degeneration.

MicroRNA-376b-3p Suppresses Choroidal Neovascularization by Regulating Glutaminolysis in Endothelial Cells.

Purpose: Choroidal neovascularization (CNV) is a common pathological change of various ocular diseases that causes serious damage to central vision. Accumulated evidence shows that microRNAs (miRNAs) are closely related with the regulation of endothelial metabolism, which plays crucial roles in angiogenesis. Here, we investigate the molecular mechanism underlying the regulation of endothelial glutamine metabolism by miR-376b-3p in the progression of CNV. Methods: Human retinal microvascular endothelial cells (HRMECs) were transfected with control or miR-376b-3p mimics, and the expression of glutaminase 1 (GLS1), a rate-limiting enzyme in glutaminolysis, was detected by real-time PCR or Western blotting. The biological function and glutamine metabolism of transfected HRMECs were measured by related kits. Luciferase reporter assays were used to validate the CCAAT/enhancer-binding protein beta (CEBPB) was a target of miR-376b-3p. Chromatin immunoprecipitation and RNA immunoprecipitation assays were performed to verify the binding of CEBPB on the promoter region of GLS1. Fundus fluorescein angiography and immunofluorescence detected the effect of miR-376b-3p agomir on rat laser-induced CNV. Results: The expression of miR-376b-3p was decreased, whereas GLS1 expression was increased in the retinal pigment epithelial-choroidal complexes of rats with CNV. HRMECs transfected with miR-376b-3p mimic showed inhibition of CEBPB, resulting in the inactivation of GLS1 transcription and glutaminolysis. Moreover, the miR-376b-3p mimic inhibited proliferation, migration and tube formation but promoted apoptosis in HRMECs, whereas these effects counteracted by α-ketoglutarate supplementation or transfection with CEBPB overexpression plasmid. Finally, the intravitreal administration of the miR-376b-3p agomir restrained CNV formation. Conclusions: Collectively, miR-376b-3p is a suppressor of glutamine metabolism in endothelial cells that could be expected to become a therapeutic target for the treatment of CNV-related diseases.

Pharmacological Inhibition of Glutaminase 1 Attenuates Alkali-Induced Corneal Neovascularization by Modulating Macrophages.

Corneal neovascularization (CoNV) in response to chemical burns is a leading cause of vision impairment. Although glutamine metabolism plays a crucial role in macrophage polarization, its regulatory effect on macrophages involved in chemical burn-induced corneal injury is not known. Here, we elucidated the connection between the reprogramming of glutamine metabolism in macrophages and the development of alkali burn-induced CoNV. Glutaminase 1 (GLS1) expression was upregulated in the mouse corneas damaged with alkali burns and was primarily located in F4/80-positive macrophages. Treatment with a selective oral GLS1 inhibitor, CB-839 (telaglenastat), significantly decreased the distribution of polarized M2 macrophages in the alkali-injured corneas and suppressed the development of CoNV. In vitro studies further demonstrated that glutamine deprivation or CB-839 treatment inhibited the proliferation, adhesion, and M2 polarization of bone marrow-derived macrophages (BMDMs) from C57BL/6J mice. CB-839 treatment markedly attenuated the secretion of proangiogenic factors, including vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor-BB (PDGF-BB) from interleukin-4- (IL-4-) regulated M2 macrophages. Our findings revealed that GLS1 inhibition or glutamine deprivation prevented alkali-induced CoNV by inhibiting the infiltration and M2 polarization of macrophages. This work suggests that pharmacological GLS1 inhibition is a feasible and effective treatment strategy for chemical burn-related CoNV in humans.

Ocular Biometric Characteristics of Chinese with History of Acute Angle Closure.

PURPOSE: To investigate the biometric characteristics of Chinese patients with a history of acute angle closure (AAC). METHODS: In this clinic-based, retrospective, observational, cross-sectional study, biometric parameters of eyes were acquired from a general population of Chinese adults. The crowding value (defined as lens thickness (LT); central corneal thickness (CCT); anterior chamber depth (ACD)/axial length (AL)) was calculated for each patient. Logistic regression analysis was performed to identify risk factors for AAC. Receiver operating characteristic (ROC) curves were plotted, and biometric variables were compared to compile a risk assessment for AAC. RESULT: This study included 1500 healthy subjects (2624 eyes, mean age of 66.54 ± 15.82 years) and 107 subjects with AAC (202 eyes, mean age of 70.01 ± 11.05 years). Eyes with AAC had thicker lens (P ≤ 0.001), shallower anterior chamber depth (P ≤ 0.001), and shorter axial length (P ≤ 0.001) than healthy eyes. Logistic regression analysis and ROC curve analysis indicated that a crowding value above 0.13 was a significant (P < 0.05) risk factor for the development of AAC. CONCLUSIONS: Biometric parameters were significantly different between the eyes from the AAC group to the normal group. Ocular crowding value might be a new noncontact screening method to assess the risk of AAC in adults.

Bioinformatics analysis to identify the differentially expressed genes of glaucoma.

The aim of the present study was to screen the differentially expressed genes (DEGs) associated with glaucoma and investigate the changing patterns of the expression of these genes. The GSE2378 gene microarray data of glaucoma was downloaded from the Gene Expression Omnibus database, which included seven normal samples and eight glaucoma astrocyte samples. Taking into account the corresponding associations between the probe ID and gene symbols, the DEGs were identified prior to and subsequent to the summation of probe level values using the Limma package in R language, followed by Gene Ontology (GO) and pathway enrichment analyses. Interaction networks of the DEGs were constructed using the Biomolecular Interaction Network Database, and cluster analysis of the genes in the networks was performed using ClusterONE. Subsequent to the summation of probe value, a total of 223 genes were identified as DEGs between the normal and glaucoma samples, including 74 downregulated and 149 upregulated genes. In addition, the DEGs were found to be associated with several functions, including response to wounding, extracellular region part and calcium ion binding. The most significantly enriched pathways were complement and coagulation cascades, arrhythmogenic right ventricular cardiomyopathy and extracellular matrix (ECM)­receptor interaction. Furthermore, interaction networks were constructed of the DEGs prior to and subsequent to the summation of probe values, and HNF4A and CEBPD were identified as hub genes. Additionally, 37 and 31 GO terms were identified to be enriched in the two DEGs of the networks prior to and subsequent to summation, respectively. The results indicated the identified genes associated with ECM as important, and the CEBPD gene was considered to be a critical gene in glaucoma. The findings of the present study offer a potential reference value in further investigations of glaucoma at the gene level.

The Relationship between Visual Field Global Indices and Retinal Nerve Fiber Layer Thickness in Healthy Myopes.

The aim of the current study was to investigate the association between the thickness of the retinal nerve fiber layer (RNFL) and central visual field indices in otherwise healthy myopes. In total, 57 otherwise healthy subjects were cross-sectionally studied. General ophthalmic examinations, refractive measurements, RNFL thickness by spectral domain optical coherence tomography (OCT), and central visual fields were examined. Linear models were used to assess the associations. In this young and mid-aged population, the mean spherical equivalent was -4.79 (SD 1.66) and -4.59 (SD 1.88) diopters in the right and left eyes, respectively. Approximately 7% to 14% of the eyes showed the average RNFL thickness out of the normal range. The temporal RNFL was remarkably thicker, whereas the nasal RNFL was thinner. The higher the refractive error, the thinner the RNFL thickness. A thicker overall RNFL was significantly associated with decreased mean sensitivity and increased mean defect, and further adjustments for age, sex, refractive error, optic disk area, or ocular magnification did not change the association. Although nonpathologic myopia does not significantly affect central visual field global indices, its effects on the RNFL may be linked with performance on the central visual field test.