CX3CL1-CX3CR1 axis protects retinal ganglion cells by inhibiting microglia activation in a distal optic nerve trauma model.

BACKGROUND: The chemokine CX3CL1 has been reported to play an important role in optic nerve protection, but the underlying mechanism is still unclear. CX3CR1, the only receptor of CX3CL1, is specifically expressed on retinal microglia, whose activation plays a role in the pathological process of optic nerve injury. This study aimed to evaluate whether CX3CL1 exerts optic neuroprotection by affecting the activation of microglia by combining with CX3CR1. METHODS: A mouse model of distal optic nerve trauma (ONT) was used to evaluate the effects of the CX3CL1-CX3CR1 axis on the activation of microglia and survival or axonal regeneration of retinal ganglion cells (RGCs). The activation of microglia, loss of RGCs, and damage to visual function were detected weekly till 4 weeks after modeling. CX3CL1 was injected intravitreally immediately or delayed after injury and the status of microglia and RGCs were examined. RESULTS: Increases in microglia activation and optic nerve damage were accompanied by a reduced production of the CX3CL1-CX3CR1 axis after the distal ONT modeling. Both immediate and delayed intravitreal injection of CX3CL1 inhibited microglia activation, promoted survival of RGCs, and improved axonal regenerative capacity. Injection with CX3CL1 was no longer effective after 48 h post ONT. The CX3CL1-CX3CR1 axis promotes survival and axonal regeneration, as indicated by GAP43 protein and gene expression, of RGCs by inhibiting the microglial activation after ONT. CONCLUSIONS: The CX3CL1-CX3CR1 axis could promote survival and axonal regeneration of RGCs by inhibiting the microglial activation after optic nerve injury. The CX3CL1-CX3CR1 axis may become a potential target for the treatment of optic nerve injury. Forty-eight hours is the longest time window for effective treatment after injury. The study is expected to provide new ideas for the development of targeted drugs for the repair of optic nerve.

Diagnostic ability of the combination of retinal microvasculature evaluation and static automated perimetry for early primary open-angle glaucoma.

PURPOSE: To investigate the diagnostic ability of retinal superficial vasculature evaluation by optic coherence tomography angiography (OCTA) combined with visual field (VF) testing for early primary open-angle glaucoma (POAG). PATIENTS AND METHODS: In this cross-sectional study, 84 participants were included, including 11 in the ocular hypertension (OHT) group, 11 in the preperimetric POAG (pre-POAG) group, 29 in the early POAG group and 33 in the control group. All participants underwent 6 × 6 mm2 scans of macula and optic nerved head by optic coherence tomography (OCT) and OCTA, along with white-on-white and blue-on-yellow VF testing by static automated perimetry. The ability of diagnosing early glaucoma by either various examinations separately or combination of examinations in both terms of function and structure was studied using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS: The superficial retinal vessel densities (VD) in peri-nasal, para-temporal, peri-temporal and peri-inferior regions around the macula, as well as vessel area densities (VAD) in all peripapillary regions, were significantly different among the four groups, with lower VD or VAD in the early POAG patients compared to the normal individuals. The diagnostic ability of peripapillary superficial retinal VAD alone or VF testing alone was limited for early POAG only. However, the combination of these two was more effective in distinguishing normal individuals from OHT subjects or pre-POAG patients without VF defects, with better performance than the combination of peripapillary retinal nerve fiber layer (RNFL) thickness and VF indicators. CONCLUSIONS: Peripapillary retinal vessel densities were generally lower in early POAG patients compared to normal individuals. The combination of peripapillary superficial retinal VAD by OCTA with white-on-white VF testing improved the ability to distinguish POAG patients at early stage without function impairment, which may help in providing reference and guidance for the following-up and treatment of suspected POAG patients.

Matrix Metalloproteinases in Glaucoma: An Updated Overview.

Matrix metalloproteinases (MMPs) are important regulators of the extracellular matrix (ECM) and are involved in many stages of cellular growth and development. An imbalance of MMP expression is also the basis of many diseases, including eye diseases, such as diabetic retinopathy (DR), glaucoma, dry eye, corneal ulcer, keratoconus. This paper describes the role of MMPs in the glaucoma and their role in the glaucomatous trabecular meshwork (TM), aqueous outflow channel, retina, and optic nerve (ON). This review also summarizes several treatments for glaucoma that target MMPs imbalance and suggests that MMPs may represent a viable therapeutic target for glaucoma.

Choroidal Microvasculature Dropout in Glaucoma.

Glaucoma is a group of diseases characterized by distinctive visual field defect and optic nerve atrophy usually associated with elevated intraocular pressure (IOP). It is one of the most serious visual disorders and the leading cause of irreversible blindness worldwide. As a multifactorial disease, the pathogenesis of glaucoma is complicated and has been far from fully understood, where vascular factors are recognized to play an important role in its development and progression of glaucoma. Empirical researches have shown that parapapillary choroidal microvasculature dropout (CMvD) is closely associated with the impairment of optic nerve head (ONH) perfusion, probably accelerating the progression of glaucoma. Accordingly, it is necessary to explore the details regarding the relationship between CMvD and glaucoma progress, hoping to enhance the understanding of pathogenesis of glaucoma. In this review, we aimed to establish comprehensive understanding of the relationship between CMvD and glaucoma with generally going through relevant up-to-date literatures. Among the events that are closely associated with CMvD, we summarized the ones specifically involved in the term of glaucomatous pathological process, including thickness of retinal nerve fiber layer (RNFL) thickness, lamina cribrosa (LC) morphology, cricumpapillary vessel density (cpVD) and visual function such as visual field (VF) defect as well as the prognosis of glaucoma. Although researchers have made great advances, there are still many issues need to be addressed particularly concerning the pathogenic role of CMvD in glaucoma development and its clinical implications with respect to glaucoma prognosis.

Establishment of a minimally invasive distal traumatic optic neuropathy model in mice to investigate cascade reactions of retinal glial cells.

Traumatic optic neuropathy (TON) is a complication of craniocerebral, orbital and facial injuries, leading to irreversible vision loss. At present, there is no reliable, widely used animal model, although it has been confirmed that TON can cause the loss of retinal ganglion cells (RGC). However, the cascade reaction of retinal glial cells underlying TON is unclear. Therefore, the establishment of an animal model to explore the pathological mechanism of TON would be of great interest to the scientific community. In this study, we propose a novel mouse model utilizing a 3D stereotaxic apparatus combined with a 27G needle to evaluate damage to the optic nerve by micro-CT, anatomy, SD-OCT and F-VEP. Immunofluorescence, western blotting, qPCR experiments were conducted to investigate the loss of RGCs and activation or inactivation of microglia, astrocytes and Müller glial cells in the retina from the first week to the fourth week after modeling. The results showed that this minimally invasive method caused damage to the distal optic nerve and loss of RGC after optic nerve injury. Microglia cells were found to be activated from the first week to the third week; however, they were inactivated at the fourth week; astrocytes were activated at the second week of injury, while Müller glial cells were gradually inactivated following injury. In conclusion, this method can be used as a novel animal model of distal TON, that results in a series of cascade reactions of retinal glial cells, which will provide a basis for future studies aimed at exploring the mechanism of TON and the search for effective treatment methods.

[Method of Dividing the Value of Soil Heavy Metal Pollution Risk Screening: Using Cd as an Example].

The Soil Environmental Quality Risk Control Standard for Soil Contamination of Agricultural Land (GB 15618-2018) provides the risk screening value of soil environmental quality in China; however, because of differences in soil composition, and physical and chemical properties in different regions, this value has limitations for certain regions. Based on the limits of pollutants in crops given in the National Food Safety Standards Limits of Pollutants for Foods (GB 2762-2017), and using Cd in the soil of the main farming areas in southeastern Chongqing as an example, the content of the elemental biological effective state was determined for the suggested screening value. This method can provide a reference and method for improving the heavy metal and healthy element thresholds of soils with high or low bioavailability, and that are rich in Se content, among other factors.