Characteristics of Retinal Vascular Degeneration and the Expression of Vessel-Related Claudin Proteins in Retinal Degeneration Mouse.

INTRODUCTION: This study aimed to investigate the characteristics of retinal vascular degeneration and the expression of vessel-related Claudin (CLD) proteins in retinal degeneration mouse ( Pde6ßrd1/rd1 rd1 mouse). METHODS: Retinas from wild-type (WT) mice and rd1 mice at postnatal day 3 (P3), P5, P8, P11, P13, P15, P18, and P21 were collected. Immunofluorescence staining was used to assess the retinal vascular plexus, cell proliferation, CLD expression, and retinal ganglion cells (RGCs). The distribution of retinal superficial and deep vessels was determined by Isolectin B4 fluorescence staining of retinal flat mounts and frozen sections. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated dNTP nick end labeling were used to investigate retinal histological degeneration and apoptosis in rd1 mice respectively. Quantitative real-time PCR and western blot were used to measure the expression of vessel-related CLD-1, 2, 3 and CLD-5, vascular endothelial growth factor A (VEGFA), and vascular endothelial growth factor receptor 2 (VEGFR2) in the retinas. RESULTS: Compared to the WT mice, the rd1 mice displayed delayed but completed progressive development in the retinal superficial vascular plexuses (SVP) and deep vascular plexuses (DVP). In the rd1 mice, the thickness of retinal layers gradually decreased and the retinas underwent progressive atrophy and degeneration. The deterioration got worse at the late developmental stage. The declined vessel density of SVP and DVP correlated with the decreased thickness of the full and inner parts of the retina and the reduced number of RGCs. DVP degeneration and the thinning of the outer nuclear layer occurred an obvious reduction at P15. The expression levels of CLD-1, CLD-2, CLD-3, CLD-5, VEGFA, and VEGFR2 decreased and were consistently lower in the rd1 mice than in WT mice since P15. CONCLUSION: Rd1 mice exhibited progressive vascular degeneration of retinal SVP and DVP, the thinning and atrophy of retinal ONL and RGC, and the downregulation of vessel-related CLD proteins during the late developmental period. Thus, the rd1 mouse is a useful model of not only retinal neuro-degeneration but also retinal vascular degeneration.

MicroRNA-124-3p Attenuated Retinal Neovascularization in Oxygen-Induced Retinopathy Mice by Inhibiting the Dysfunction of Retinal Neuroglial Cells through STAT3 Pathway.

MicroRNA (miRNA) is a non-coding RNA that can regulate the expression of many target genes, and it is widely involved in various important physiological activities. MiR-124-3p was found to associate with the normal development of retinal vessels in our previous study, but the mechanism of its anti-angiogenic effect on pathological retinal neovascularization still needed to be explored. Therefore, this study aimed to investigate the effect and mechanism of miR-124-3p on retinal neovascularization in mice with oxygen-induced retinopathy (OIR). Here, we found that intravitreal injection of miR-124-3p agomir attenuated pathological retinal neovascularization in OIR mice. Moreover, miR-124-3p preserved the astrocytic template, inhibited reactive gliosis, and reduced the inflammatory response as well as necroptosis. Furthermore, miR-124-3p inhibited the signal transducer and activator of transcription 3 (STAT3) pathway and decreased the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor. Taken together, our results revealed that miR-124-3p inhibited retinal neovascularization and neuroglial dysfunction by targeting STAT3 in OIR mice.

Cortical functional networks of transcutaneous electrical stimulation at acupoints on the pericardial meridian.

To explore the relationship between pericardial meridian acupoints and brain, the electroencephalogram (EEG) signals were collected synchronously during transcutaneous electrical stimulation at PC3, PC5, PC7, and PC8 on the pericardial meridian in 21 healthy subjects. The cerebral cortex functional networks were constructed by standard low-resolution electromagnetic tomography (sLORETA), phase-locking value (PLV) and complex network methods. The prefrontal cortex (BA10), the orbitofrontal cortex (BA11), the middle temporal gyrus (BA21), the temporal gyrus (BA22), the temporal pole (BA38), the triangular part (BA44), the dorsolateral prefrontal cortex (BA46), and the inferior frontal cortex (BA47) were activated by electrical stimulation at PC3, PC5, PC7, and PC8 on the pericardium meridian. These activated brain regions are able to modulate both local and remote emotion and cognitive networks. Acupoint stimulation of pericardium meridian mainly activated the frontal and the temporal lobes. Compared with non-acupoint stimulation, the node degree in the frontal lobe of electrical stimulation at PC3 (p < 0.05), PC5 (p < 0.05), PC7 (p < 0.01), PC8 (p < 0.05) and the temporal lobe of PC3 (p < 0.05), PC5 (p < 0.05), PC7 (p < 0.05), PC8 (p < 0.01) were significantly increased. The clustering coefficient in the frontal lobe of the stimulation at PC3 (p < 0.05), PC5 (p < 0.05), PC7 (p < 0.01), PC8 (p < 0.05) and the temporal lobe of PC3 (p < 0.05), PC5 (p < 0.05), PC7 (p < 0.01), PC8 (p < 0.05) were significantly increased. The characteristic path length decreased and the global efficiency increased during acupoint stimulation. The changes of functional network of stimulated pericardium meridian through cerebral cortex may provide theoretical support for the specificity of meridian and acupoints.

Cerebral cortex Functional Networks of Transdermal Electrical Stimulation at Daling (PC7) Acupoint.

The cerebral cortex functional network of Electroencephalogram (EEG) signals during transcutaneous electrical acupoint stimulation (TEAS) on 21 healthy subjects was constructed by using three modules: standard low-resolution brain electromagnetic tomography (sLORETA), phase-locking value (PLV), and complex network. We investigated the brain functional network triggered by PC7 stimulation by comparing with resting state and non-acupoint stimulation. The results showed that the PC7 stimulation mainly activated frontal lobe and temporal lobe including prefrontal cortex (BA10), insular lobe (BA13), temporal gyrus (BA22), anterior cingulate cortex (BA32), temporal pole (BA38), dorsolateral prefrontal cortex (BA46), and inferior frontal cortex (BA47), which are all closely linked to cognition, spirit, and emotion in brain. Furthermore, the degrees of node in frontal, temporal, and whole brain are increased significantly or extreme significantly with p < 0.05, p < 0.05, and p < 0.01, respectively; clustering coefficient in frontal, temporal, and whole brain are all statistically significant (p < 0.05). The information transmission efficiency of cerebral cortex has been greatly improved. During PC7 stimulation, the topological changes in the activation of cerebral regions and cortical functional networks are consistent with the therapeutic effect, which may provide theoretical support for acupoint stimulation to regulate nerve function.

The Change of Aqueous Humor Cytokine Levels after Anti-VEGF in Diabetic Macular Edema: A Systematic Review and Meta-Analysis.

Background: Diabetic macular edema (DME) is a vision-threatening complication that severely impairs vision, and VEGF has a certain improvement effect on it as a growth factor. Objective: To assess the alterations of different aqueous humor cytokine concentrations after intravitreal antivascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). Methods: We searched PubMed, EMBASE, and the Cochrane Library from inception up to May 2022 for studies evaluating the alterations of different aqueous humor cytokine concentrations after intravitreal anti-VEGF treatment for diabetic macular edema. The estimates from eligible studies were meta-analyzed by the Hartung-Knapp/Sidik-Jonkman random-effects method. Egger's regression test was used to determine the publications' bias. A 95% confidence interval was calculated across studies. The analysis was performed using STATA™ Version 15 software. Results: Nine eligible studies involving a total of 209 eyes for our systematic review were identified through our search strategy. The mean differences in 1-month and 2-month changes of VEGF were 110.681 pg/ml (P < 0.001) and 283.474 pg/ml (P=0.003), respectively. The mean difference in 2-month changes of interleukin 6 (IL-6) was -24.784 pg/ml (P=0.037). The mean difference in 3-month changes of central macular thickness was 130.372 µm (P < 0.001). Conclusions: Intravitreal injection of anti-VEGF exerts a protective effect on macular edema secondary to diabetic retinopathy by affecting various cytokine concentrations, especially reducing aqueous VEGF concentrations and interleukin 6 in patients with DME.

Electroencephalogram Analysis of Magnetic Stimulation at Different Acupoints.

Magnetic stimulation has some similarities with acupuncture, and it has broad application prospects because of its non-invasiveness and easy quantification. This paper combines magnetic stimulation technology with electroencephalography to analyze the time-frequency and the brain functional network results elicited by magnetic stimulation at different acupoints. This paper hopes to observe the different effects of stimulating different acupoints on the brain from the perspective of EEG. The EEG signals during magnetic stimulation at ST36, ST40, and GB37 were recorded, respectively. The time-frequency results showed that the magnetic stimulation at ST36 and ST40 on the Foot Yangming Stomach Meridian increased the energy in the left parietal lobe and the right central region, and the energy increased mainly in the theta and alpha bands. However, during the magnetic stimulation at GB37 on the Foot Shaoyang Gallbladder Meridian, the energy in the central region and the frontal lobe increased, and the energy increased mainly in the delta, theta, and alpha bands. Moreover, the energy in the right parietal lobe decreased during magnetic stimulation at GB37. The results of brain functional network were also consistent with time-frequency results. The brain network connections of GB37 stimulation in the central region were significantly less than that of ST36 and ST40 (p < 0.01). In addition, the connections between central region and frontal lobe and the connections between central region and parietal lobe of GB37 stimulation were significantly different from that of ST36 and ST40 (p < 0.01). The above results indicate that ST36 and ST40 on the same meridian have similar effects on the brain, while GB37 on the other meridian has completely different effects from ST36 and ST40. The results of this paper explain the reason why stimulating ST36 and ST40 can treat similar diseases from the perspective of EEG, and also explain that stimulating GB37 has significantly different effects on the brain from that of ST36 and ST40.

The Imaging Characteristics of Lens Subluxation on the Ultrasound Biomicroscopy.

Background: To evaluate the imaging characteristics of the lens subluxation with the use of ultrasound biomicroscopy. Methods: From October 2018 to September 2019, 55 eyes diagnosed with lens subluxation were enrolled in the group. All patients underwent detailed eye examination and panoramic ultrasound biomicroscopy. Results: The most common sites of lens suspensory ligament injury were superior temporal side (32.73%) and superior nasal side (23.63%). The most common range of subluxation in all patients was 30°. Comparing the measurement indicators of all patients, ciliary body thickness (CBT) in affected eyes was smaller than that in healthy eyes (0.79 ± 0.21, 1.04 ± 0.16), the distance between ciliary process and crystal equator increased (1.91 ± 0.70, 1.17 ± 0.32), and iris-ciliary processes distance (ICPD) increased (1.04 ± 0.51, 0.80 ± 0.17) (P < 0.05). The range of subluxation in patients with lens subluxation was positively correlated with the distance between ciliary processes and the crystal equator. Conclusions: The ultrasound biological microscope has a good application significance in the diagnosis of lens subluxation. From this study, we suggest that the three indexes of CBT, ICPD, and the distance between the ciliary process and crystal equator are of high reference value in ultrasound biomicroscopy among patients with lens subluxation.