Qing Yuan

Rhamnazin attenuates inflammation and inhibits alkali burn-induced corneal neovascularization in rats

The purpose of our study was to determine whether rhamnazin inhibits corneal neovascularization in the rat alkali burn model, and alleviates the inflammatory response of the cornea. Rhamnazin inhibited the proliferation of HUVEC cells in a dose-dependent manner, and it also inhibited the migration and luminal formation of HUVEC cells. 20 μM rhamnazin eye drops were applied to an animal model of corneal alkali burn neovascularization 4 times a day for 14 days. The corneal neovascularization in the rhamnazin group was obviously less than that in the PBS control group. In the rhamnazin group, the inflammatory index of the cornea decreased gradually over time, whereas the inflammatory index of the PBS group decreased only slightly with time. The corneal CNV area in the PBS group was significantly larger than that in the rhamnazin group. The expression level of VEGF protein of the rhamnazin group was lower than that in the PBS group, and the expression level of PEDF was significantly higher than that of the PBS group. Rhamnazin downregulated the expression of VEGFR2 protein and decreased the expression levels of p-STAT3, p-MAPK and p-Akt proteins. This study provides a new idea for the study of the molecular mechanism of corneal neovascularization.

Comparative study of interhemispheric functional connectivity in left eye monocular blindness versus right eye monocular blindness: a resting-state functional MRI study

Objective In the present study, we investigated the brain interhemispheric functional connectivity changes in left eye MB versus right eye MB patients by voxel-mirrored homotopic connectivity (VMHC) methods. Methods A total of 31 patients with MB (15 with left eye MB and 16 with right eye MB), and 31 healthy controls (HCs) closely matched for age were recruited. All subjects underwent functional magnetic resonance imaging (fMRI) examinations. The VMHC method was used to evaluate directly functional interactions between the hemispheres. A one-way ANOVA was performed to determine the regions in which the VMHC differs between the three groups. Patients with MB were distinguished from HCs by a receiver operating characteristic (ROC) curve. The relationships between the mean VMHC signal values in many brain regions and clinical features in MB patients were calculated by pearson correlation analysis. Results Compared with HCs, MB patients had significantly decreased VMHC values in the cuneus/calcarine/lingual gyrus. Furthermore, left eye MB showed decreased VMHC values in the cuneus/calcarine/lingual gyrus and showed increased VMHC values in the insula and middle frontal gyrus compared with HC. In addition, right eye MB showed decreased VMHC values in the cuneus/calcarine/lingual gyrus, primary motor cortex (M1)/primary somatosensory cortex (S1) and superior parietal lobule. Conclusion MB subjects showed abnormal brain interhemispheric functional connectivity in visual pathways. Furthermore, different patterns of brain interhemispheric functional connectivity occurred in the left eye and right eye MB. These VMHC values provide much useful information to explain the neural mechanism changes in MB.

Altered spontaneous brain activity patterns in strabismus with amblyopia patients using amplitude of low-frequency fluctuation: a resting-state fMRI study

Objective Previous studies have demonstrated that strabismus or amblyopia can result in markedly brain function and anatomical alterations. However, the differences in spontaneous brain activities of strabismus with amblyopia (SA) patients still remain unclear. This current study intended to use the amplitude of low-frequency fluctuation (ALFF) technique to investigate the intrinsic brain activity changes in SA subjects. Patients and methods A total of 16 patients with SA (6 males and 10 females) and 16 healthy controls (HCs; 6 males and 10 females) similarly matched in age, gender, and education status were recruited and examined with the resting-state functional MRI. The spontaneous brain activity changes were investigated using the ALFF technique. The receiver operating characteristic curve was performed to classify the mean ALFF signal values of the SA patients from HCs. The correlations between the ALFF values of distinct brain regions and the clinical manifestations in SA patients were evaluated in terms of the Pearson’s correlation analysis. Results Compared with HCs, SA patients had significantly decreased ALFF in the left cerebellum posterior lobe, left middle frontal gyrus, and bilateral thalamus. In contrast, SA patients showed increased ALFF values in the right superior frontal gyrus, right precuneus, left cuneus, and bilateral precentral gyrus. Nonetheless, there was no linear correlation between the mean ALFF values in brain regions and clinical features. Conclusion Diverse brain regions including vision-related and motion-related areas exhibited aberrant intrinsic brain activity patterns, which imply the neuropathologic mechanisms of oculomotor disorder and vision deficit in the SA patients.

Altered intrinsic brain activities in patients with acute eye pain using amplitude of low-frequency fluctuation: a resting-state fMRI study

Objective Many previous studies have reported that pain symptoms can lead to significant brain function and anatomical changes, whereas the intrinsic brain activity changes in acute eye pain (EP) patients remain unknown. Using the amplitude of low-frequency fluctuation (ALFF) method, this study aimed to evaluate the spontaneous brain activity alterations and their relationships with clinical features in acute EP patients. Participants and methods A total of 20 patients with EP (15 males and 5 females) and 20 healthy controls (HCs; 15 males and 5 females) closely matched in age, sex, and education underwent resting-state functional magnetic resonance imaging scans. The ALFF method was applied to assess spontaneous brain activity changes. The ALFF values of the EP patients were distinguished from those of the HCs using a receiver operating characteristic curve. Pearson’s correlation analysis was used to investigate the relationships between the mean ALFF signal values from many brain regions and the clinical features in EP patients. Results Compared with the HCs, acute EP patients had significantly lower ALFF in the left and right precentral/postcentral gyrus and left precuneus. In contrast, acute EP patients showed higher ALFF values in the right and left parahippocampal gyri and left caudate. However, no relationship was observed between the mean ALFF signal values from the different areas and clinical manifestations in the acute EP patients. Conclusion We demonstrated that acute EP patients showed abnormal intrinsic brain activities in the precentral/postcentral gyrus and limbic system, which might provide useful information for explaining neural mechanisms in EP patients.

Resting cerebral blood flow alterations specific to the comitant exophoria patients revealed by arterial spin labeling perfusion magnetic resonance imaging

PURPOSEnIt has been shown in many previous studies that there were significant changes of the brain anatomy and function in strabismus. However, the significance of the alterations of resting cerebral blood flow (CBF) in comitant exophoria (CE) remains obscure. Arterial spin labeling (ASL) MRI, which is a noninvasive method, could be applied to detect the cerebral blood flow quantitatively. Our study aimed to compare the resting CBF between the comitant exophoria and health controls using pseudo-continuous arterial spin labeling (pCASL) perfusion MRI method.nnnMETHODSn32 patients (25 males and 7 females) with CE (study group), and 32 (25 males and 7 females) healthy individuals with matched age and sex status (control group) underwent a whole-brain pCASL magnetic resonance (MR) examination at the resting state. The resting CBF were voxel-wise compared between the two groups using an analysis of variance designed in a statistical parametric mapping program. The CE patients were distinguishable from the healthy controls (HCs) by receiver operating characteristic (ROC) curves.nnnRESULTSnCompared with the control group, the CE group showed significantly increased resting CBF values in the right parahippocampal regions, bilateral medial frontal gyrus/anterior cingulate cortex, left inferior frontal gyrus, right inferior frontal gyrus, left superior frontal gyrus, bilateral medial cingulate cortex, right middle frontal gyrus, and right paracentral lobule.nnnCONCLUSIONnComitant exophoria showed increased resting CBF in eye movement-related brain areas including supplementary eye field, cingulate eye field and frontal eye field, which could be an explanation of the brain function compensation for the ocular motility disorders in the CE patients.

Assessment of synchronous neural activities revealed by regional homogeneity in individuals with acute eye pain: a resting-state functional magnetic resonance imaging study

Objective Previous neuroimaging studies have demonstrated that pain-related diseases are associated with brain function and anatomical abnormalities, whereas altered synchronous neural activity in acute eye pain (EP) patients has not been investigated. The purpose of this study was to explore whether or not synchronous neural activity changes were measured with the regional homogeneity (ReHo) method in acute EP patients. Methods A total of 20 patients (15 males and 5 females) with EP and 20 healthy controls (HCs) consisting of 15 and 5 age-, sex-, and education-matched males and females, respectively, underwent resting-state functional magnetic resonance imaging. The ReHo method was applied to assess synchronous neural activity changes. Results Compared with HCs, acute EP patients had significantly lower ReHo values in the left precentral/postcentral gyrus (Brodmann area [BA]3/4), right precentral/postcentral gyrus (BA3/4), and left middle frontal gyrus (BA6). In contrast, higher ReHo values in acute EP patients were observed in the left superior frontal gyrus (BA11), right inferior parietal lobule (BA39/40), and left precuneus (BA7). However, no relationship was found between the mean ReHo signal values of the different areas and clinical manifestations, which included both the duration and degree of pain in EP patients. Conclusion Our study highlighted that acute EP patients showed altered synchronous neural activities in many brain regions, including somatosensory regions. These findings might provide useful information for exploration of the neural mechanisms underlying acute EP.

Xanthatin inhibits corneal neovascularization by inhibiting the VEGFR2‑mediated STAT3/PI3K/Akt signaling pathway

Alkali burn is one of the main causes of corneal injury. The inflammation and neovascularization caused by alkali burns aggravate corneal damage, resulting in loss of vision. The aim of the present study was to evaluate the efficacy of xanthatin in the treatment of alkali burn-induced inflammation and neovascularization. A CCK-8 assay was used to detect the effects of different concentrations of xanthatin on the proliferation of human umbilical vein endothelial cells (HUVECs). The effects of xanthatin on the migration of HUVECs and the ability of lumen formation were examined using a scratch test and lumen formation assay, respectively. A total of 60 Sprague-Dawley rats were randomly divided into two groups to establish a corneal alkali burn model, and were treated with PBS and xanthatin eye drops four times a day. A slit lamp microscope recorded changes of the cornea at 0, 4, 7, 10 and 14 days, and the inflammatory indices of the cornea and the neovascular area were evaluated. The expression levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in the cornea under different treatment conditions were detected using immunofluorescence and western blot analysis. In order to investigate the mechanism of xanthatin on the inhibition of inflammation and neovascularization, HUVECs were treated with xanthatin and PBS following VEGF treatment. The subcellular localization of signal transducer and activator of transcription 3 (STAT3) was detected using immunofluorescence. The expression levels of VEGF receptor 2 (VEGFR2), STAT3, phosphoinositide 3-kinase (PI3K) and Akt were detected using western blot analysis. The results revealed that xanthatin inhibited the proliferation of HUVECs in a concentration-dependent manner. The migration ability and lumen-forming ability of the HUVECs were also inhibited by xanthatin. Slit lamp microscopy showed that the inflammatory index and the area of neovascularization in the xanthatin-treated group were significantly reduced, compared with those in the PBS treatment group. The xanthatin treatment group exhibited a lower protein expression level of VEGF and increased protein expression level of PEDF, compared with the PBS treatment group. In the VEGF-treated HUVECs, xanthatin significantly decreased the expression levels of p-VEGFR2, phosphorylated (p-)STAT3, p-PI3K and p-Akt. In conclusion, the present study confirmed that xanthatin inhibited corneal neovascularization and inflammation in the alkali burn model, elucidating the underlying mechanisms involved in its protective effects. Therefore, xanthatin may be a novel drug for the treatment of corneal alkali burn.

The role of pirfenidone in alkali burn rat cornea

ABSTRACT To evaluate the effects of pirfenidone in the treatment of HUVEC using an in vitro model and on rat corneal wound healing, edema, cornea neovascularization (CNV) and inflammation after alkali burn in vivo model. In vitro, CCK‐8 assay was used to detect the effect of pirfenidone on the viability of HUVECs. The effects of pirfenidone on migration and tube formation of HUVEC were evaluated by HUVEC cell wound closure and tube formation assay. In vivo, Eye drops containing pirfenidone or phosphate buffered saline (PBS) were administered to an alkali‐burn‐induced corneal inflammatory and neovascularization model four times daily. The clinical evaluations, including fluorescent staining and cornea edema, were performed on days 1, 4, 7 and 14 using slit lamp microscopy. Global specimens were collected on day 7 and processed for immunofluorescent staining Collagen IV, &agr;‐smooth muscle actin (&agr;‐SMA), vascular endothelial growth factor (VEGF), pigment epithelium derived factor (PEDF) and cluster of differentiation34 (CD34). The levels of &agr;‐SMA, VEGF, PEDF, CD34, CD31 and nuclear factor‐kappa B (NF‐&kgr;B) proteins in the corneas were determined by western blot. Pirfenidone affects HUVEC viability, migration and tube formation in a dose‐dependent manner. High concentration of pirfenidone can inhibit HUVEC viability, migration and tube formation in vitro and reduce alkali burn rat cornea edema, promote corneal wound healing, inhibit CNV and inflammation after alkali burn in vivo. Pirfenidone promotes corneal wound healing, and inhibits cornea neovascularization and inflammation after alkali burn in vitro and in vivo. Pirfenidone may be the potential anti‐inflammation agent for the clinical treatment of CNV. HighlightsPirfenidone affects HUVEC viability, migration and tube formation in a dose‐dependent manner;High concentration of pirfenidone can inhibit HUVEC viability, migration and tube formation and reduce alkali burn rat cornea edema, promote corneal wound healing, inhibit cornea neovascularization and inflammation;Pirfenidone promotes corneal wound healing, and inhibits cornea neovascularization and inflammation after alkali burn;Pirfenidone may be the potential anti‐inflammation agent for the clinical treatment of CNV.

RETINAL MICROVASCULATURE ALTERATION IN ACTIVE THYROID-ASSOCIATED OPHTHALMOPATHY

OBJECTIVEnIt is uncertain whether there is an increased retinal vessel density in patients with thyroid-associated ophthalmology (TAO), or if ocular hemodynamic changes are associated with their vision. Many techniques have been applied to analyze ocular hemodynamic changes in TAO patients; however, they suffer from limitations. Optical coherence tomography angiography (OCTA) is more sensitive to hemodynamic changes. We performed OCTA to determine whether there is an increased retinal vessel density in TAO patients, and investigate associations with their vision.nnnMETHODSnTwenty TAO patients (right eye) and 20 normal controls (right eye) were recruited for the study. Three-dimensional OCTA images were generated with 6 × 6-mm angiographic OCT scans of the superficial retinal layer (SRL) and deeper retinal layer (DRL) of the macular retina for each eye. We calculated the microvascular (MIR) and macrovascular (MAR) densities and compared MIR, MAR, and total MIR (TMI) density in the healthy control and TAO groups separately. We used the annular partition (C1-C6) and quadrant partition method to analyze retinal vessel density alterations. Correlation analyses were used to examine the association of MIR density and visual acuity.nnnRESULTSnIn the SRL, STMI (superficial TMI) and SMIR (superficial MIR) density increased in the macular area of TAO patients ( P<.05). For the DRL, the density of DMIR (deeper MIR) increased in macular area only ( P<.05). However, with the annular partition method, TAO patients showed significantly increased SMIR density in the C1 and C2 regions ( P<.05), and increased DMIR density only in the C1 region ( P<.05). In the SRL, the correlation coefficient of the STMI/SMIR density in the TAO group was -0.538 ( r = -0.538, P = .032), and visual acuity was -0.624 ( r = -0.624, P = .010).nnnCONCLUSIONnOCTA findings suggest that active TAO patients present with an increased retinal MIR density. Moreover, increased macular STMI and SMIR density might affect visual acuity.nnnABBREVIATIONSnCDI = color Doppler imaging; DMIR = deeper MIR; DRL = deeper retinal layer; EDV = end diastolic velocity; FAZ = foveal avascular zone; GO = Graves ophthalmopathy; MAR = macrovascular; MIR = microvascular; OCT = optical coherence tomography; OCTA = optical coherence tomography angiography; RI = resistance index; ROC = receiver operating characteristic; SMIR = superficial MIR; SOV = superior ophthalmic vein; SRL = superficial retinal layer; SSADA = split-spectrum amplitude-decor-relation angiography; STMI = superficial TMI; TAO = thyroid-associated ophthalmology; TMI = total MIR.

Retinal microvasculature alteration in central serous chorioretinopathy

The aim of the present study was to investigate the changes of retinal microvascular network in patients with central serous chorioretinopathy (CSCR). A total of fifteen patients (right eye) with CSCR and 15 normal controls (right eye) were recruited. We used optical coherence tomography angiography to scan 6×6 mm macular retinal blood flow images with the application of a series of customized image segmentation processing program software to obtain microvascular and macrovascular density, and compared the superficial microvascular (SMIR), superficial macrovascular ring (SMAR) and the superficial total microvascular (STMI) density between CSCR patients and control group. Using the annular partition (C1-C6) and quadrant partition methods on the macular, we compared the retinal vessel density changes. We also performed ROC analysis of superficial retinal microvessel density in CSCR retina to investigate the relationship between the microvascular density, the foveal thickness and visual acuity. The density of STMI and SMIR decreased in macular area in the patients with CSCR compared to the normal controls (P<0.05), while the density of SMAR did not change significantly. We found no significant difference in the density of SMIR with the quadrant partition method, whereas the annular partition method showed significantly decreased SMIR density only in the C1 region in patients with CSCR (P<0.05), with no significant difference observed in C2-C6 regions. The density of SMIR had the highest differentiation power in the CSCR group, whereas the density of SC1 ring had the lowest differentiation power by the annular method. The largest area under the ROC curves was 0.77. The correlation index of the SMIR density and visual acuity was −0.544, whereas macular thickness and visual acuity was −0.644 in the CSCR group. The density of STMI and SMIR were decreased in patients with CSCR, which might provide further understanding of the pathogenesis of CSCR.