Herpes Simplex Virus Type 1 Infection Induces the Formation of Tunneling Nanotubes.

Herpes simplex virus type 1 (HSV-1) is human specific virus. The intercellular transmission of HSV-1 is essential in its pathogenesis. The tunneling nanotube (TNT), a new mode connecting distant cells, has been found to play an important role in the spread of various viruses like human immunodeficiency virus (HIV) and influenza virus. However, whether HSV-1 can be transmitted through TNTs has not been confirmed. The purpose of this study was to clarify this, and further to determine the effect of inhibiting the actin-related protein 2/3 (Arp2/3) complex on the intercellular transmission of HSV-1. A scanning electron microscope and fluorescence microscope detected the formation of TNTs between HSV-1 infected cells. Envelope glycoprotein D (gD) and envelope glycoprotein E (gE) of HSV-1 and viral particles were observed in TNTs. Treatment with CK666, an inhibitor of the Arp2/3 complex, reduced the number of TNTs by approximately 40-80%. At the same time, the DNA level of HSV-1 in cells and the number of plaque formation units (PFU) were also reduced by nearly 30%. These findings indicated that TNT contributes to HSV-1 transmission and that the inhibition of the Arp2/3 complex could impair HSV-1 transmission, which not only provides a novel insight into the transmission mode of HSV-1, but also a putative new antiviral target.

Comparative analysis of OCT-defined parapapillary beta and gamma zones between primary open angle glaucoma and primary angle closure glaucoma.

The ophthalmoscopic beta zone of parapapillary atrophy has recently been proposed to divide into a gamma zone and a (new) beta zone based on OCT imaging. The present study was undertaken to compare the microstructural characteristics of parapapillary gamma and beta zones and their influencing factors between primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG). Seventy-three PACG patients that had no evidence of an acute attack and 78 POAG patients were enrolled. Patients were matched by propensity scores for age and visual field mean defect (MD) value. The area and angular extent of both zones were measured. In multivariate analysis, a larger beta zone was correlated with older age, severe MD value and longer axial length. A larger gamma zone was correlated with longer axial length. Older age and severe MD value were correlated with the concentric shape of beta zone. Comparing the PACG and POAG groups that adjusted for age and MD value, gamma zone was larger and more prevalent in the POAG group, while beta zone showed no significant difference. Taken separately, MD value was associated with the area and shape of beta zone in the PACG group. Axial length was associated with the temporal shape of beta zone in the POAG group. These data indicated that OCT-defined parapapillary beta and gamma zones exhibited different characteristics in two types of glaucoma. Clinically, the size of parapapillary beta zone may serve as a better indicator of glaucoma severity in eyes with PACG than that in POAG.

Effect of Nimodipine on Macular and Peripapillary Capillary Vessel Density in Patients with Normal-tension Glaucoma Using Optical Coherence Tomography Angiography.

PURPOSE: This study aimed to investigate the effect of nimodipine on peripapillary and macular capillary vessel density (VD) in patients with normal-tension glaucoma (NTG) using optical coherence tomography angiography (OCTA). METHODS: Sixty mg nimodipine was administered to 20 enrolled NTG patients for 3 months. Patients were treated with glaucoma medication simultaneously. The macular and peripapillary VD were measured automatically by OCTA at baseline, 1.5 h after administering nimodipine, and after 3 months of administering the drug. The retinal nerve fibre layer (RNFL), ganglion cell complex thickness, visual field (VF) testing, intraocular pressure (IOP), blood pressure and pulse rate in each subject were assessed during each follow-up. RESULTS: Compared with the baseline, the parafovea VD was higher (50.89 ± 4.26 versus 46.80 ± 5.40, P = .044) 1.5 h after administration of nimodipine. After administration of nimodipine for 3 months, the parafovea VD was obviously increased (51.14 ± 5.68 versus 46.80 ± 5.40, P = .039), while IOP, systolic blood pressure, mean arterial pressure and mean ocular perfusion pressure were decreased compared to baseline (all P < .05). No significant differences were found between the radial peripapillary capillary and disc VD. The parafovea VD was positively correlated with the administration of nimodipine (ß = 0.39, P = .004), RNFL thickness (ß = 0.49, P = .022), and VF mean deviation (ß = 0.4, P = .040) in the multivariate analysis. CONCLUSIONS: Nimodipine effectively increased superficial macular capillary VD, but did not affect peripapillary capillary VD in patients with NTG. This finding indicates that patients with NTG may benefit from the administration of nimodipine.

Clinical features of microvasculature in subzones of parapapillary atrophy in myopic eyes: an OCT-angiography study.

PURPOSE: To investigate the microvasculature in subzones of parapapillary atrophy (PPA) and their associated factors in healthy myopic eyes using optical coherence tomography (OCT) angiography. METHODS: The cross-sectional study included 55 healthy myopic eyes with PPA. The superficial radial peripapillary capillary (RPC) and choroidal microvascular densities were delineated and measured in alpha, beta, and gamma zone PPA using OCT angiography, respectively. The structural parameters including the width and area in each subzone and corresponding retinal nerve fiber layer thickness were further measured. Statistical analysis was performed to explore the relationship between the vascular and structural parameters. RESULTS: The mean age and mean axial length of the participants were 27.55 ± 5.72 years and 25.19 ± 1.08 mm. Among alpha, beta, and gamma zone PPA, the beta zone showed the lowest RPC density, which was negatively correlated with the area and width of beta zone (P < 0.05). The gamma zone showed the highest RPC density, which was positively correlated with the retinal nerve fiber layer thickness of gamma zone (P < 0.01). Compared with alpha zone, both gamma and beta zones showed marked decrease of choriocapillaris. The beta zone showed a lower choroidal microvascular density than that of gamma zone (P < 0.01). Choroidal microvascular density in beta and gamma zones were negatively correlated with the width of beta zone and gamma zone, respectively (P < 0.01). CONCLUSIONS: Topographic differences on superficial RPC and choroidal microvasculature were found among the subzones of PPA. A microcirculatory deficiency in beta zone PPA may exist in myopic eyes.

Morphological features of parapapillary beta zone and gamma zone in chronic primary angle-closure glaucoma.

PURPOSE: To investigate the morphological features of parapapillary beta zone and gamma zone and their associated factors in eyes with chronic primary angle-closure glaucoma (CACG). METHODS: The observational cross-sectional study included 65 CACG eyes and 65 non-myopic control eyes. On enhanced depth imaging of optical coherent tomography images, the area of parapapillary beta zone and gamma zone, and the peripapillary choroidal thickness at 6 sectors were measured. The optic disc ovality index and Bruch's membrane opening (BMO) shape were further calculated. RESULTS: Beta zone was present in 103 (79.2%) eyes and gamma zone in 29 (22.3%) eyes. Compared to control eyes, CACG was associated with larger parapapillary beta zone, female gender, and older age (P < 0.01). No significant difference was observed in axial length and peripapillary choroidal thickness between both groups (P > 0.05). In multivariate analysis, beta zone area was positively associated with older age and higher prevalence of CACG (P < 0.01), while a larger gamma zone area was associated with a smaller disc ovality index and a higher BMO ovality ratio (P < 0.01). The peripapillary choroidal thickness at six sectors was decreased with older age (P < 0.01). CONCLUSIONS: In mainly non-myopic subjects with or without CACG, larger parapapillary beta zone was correlated with older age and presence of glaucoma, while a larger parapapillary gamma zone was correlated with disc ovality but not with glaucoma. Parapapillary beta zone and gamma zone may play different roles in physiological and glaucomatous changes around optic nerve head.

Optic disc shape in patients with long-lasting unilateral esotropia and exotropia.

BACKGROUND: Horizontal eye movements have been proposed to induce biomechanical stress and strain on optic nerve head. Since strabismus may lead to sustained adduction or abduction, we investigate the effects of long lasting unilateral horizontal strabismus on the morphology of optic disc. METHODS: The observational cross-sectional study included patients with unilateral constant horizontal strabismus lasting for more than two years. The patients underwent an ophthalmological examination including refraction and morphometry of the optic nerve head. A prism cover test using right angle glass prism was performed to measure the magnitude of the ocular deviation. RESULTS: The study included 70 patients with a unilateral constant strabismus (35 esotropic patients, 35 exotropic patients) with a mean age of 26 ± 19 years, mean refractive error of - 0.72 ± 3.3 diopters, mean axial length of 23.8 ± 1.7 mm, and a mean angle of deviation of 87 ± 36 prism diopters (Chinese right-angle glass method) in the esotropic group and - 97 ± 29 prism diopters in the exotropic group. In the whole study population and taken separately in the esotropic group and exotropic group, the disc ovality index (defined as ratio of minimal-to-maximal optic disc diameter) did not differ significantly between the deviating eyes and the contralateral fixating eyes (all P > 0.05). As a corollary, the disc ovality index and the prevalence of parapapillary beta/gamma zone did not differ significantly between the esotropic group and the exotropic group (all P > 0.05). CONCLUSIONS: Optic disc ovality did not differ markedly among long-lasting esotropic eyes, exotropic eyes, and non-strabismic eyes. It suggests that optic disc shape may not be markedly influenced in non-highly myopic eyes by a potential backward pull of the optic nerve on the optic disc structures in adduction or abduction.

Overexpression of Optic Atrophy Type 1 Protects Retinal Ganglion Cells and Upregulates Parkin Expression in Experimental Glaucoma.

Glaucoma is a neurodegenerative disease that features progressive loss of retinal ganglion cells (RGCs). Increasing evidences have revealed that impaired mitochondrial dynamics occurs early in neurodegenerative diseases. Optic Atrophy Type 1 (OPA1), a mitochondrial fusion protein, has recently been suggested to be a mitophagic factor. Our previous studies found that glaucomatous retinal damage may be ameliorated by an increase in mitochondrial OPA1. In this study, we explored the mechanism involved in OPA1 mediated neuroprotection and its relationship with parkin dependent mitophagy in experimental glaucoma models. Our data showed that overexpression of OPA1 by viral vectors protected against RGC loss, attenuated Bax expression, and improved mitochondrial health and mitochondrial surface area. Parkin expression and the number of mitophagosomes were upregulated in OPA1 overexpressed RGCs under glutamate excitotoxicity. While knockdown of OPA1 by siRNA decreased protein expression of parkin in RGCs under glutamate excitotoxicity. Two weeks after intraocular pressure (IOP) elevation, the LC3-II/I ratio and the LAMP1 expression were increased in OPA1 overexpressed optic nerve. These findings suggest that OPA1 overexpression may protect RGCs by ways of enhancing mitochondria fusion and parkin mediated mitophagy. Interventions to promote mitochondrial fusion and mitophagy may provide a useful strategy to battle against glaucomatous RGC loss.