Microglial repopulation restricts ocular inflammation and choroidal neovascularization in mice.

Introduction: Age-related macular degeneration (AMD) is a prevalent, chronic and progressive retinal degenerative disease characterized by an inflammatory response mediated by activated microglia accumulating in the retina. In this study, we demonstrate the therapeutically effects and the underlying mechanisms of microglial repopulation in the laser-induced choroidal neovascularization (CNV) model of exudative AMD. Methods: The CSF1R inhibitor PLX3397 was used to establish a treatment paradigm for microglial repopulation in the retina. Neovascular leakage and neovascular area were examined by fundus fluorescein angiography (FFA) and immunostaining of whole-mount RPE-choroid-sclera complexes in CNV mice receiving PLX3397. Altered cellular senescence was measured by beta-galactosidase (SA-ß-gal) activity and p16INK4a expression. The effect and mechanisms of repopulated microglia on leukocyte infiltration and the inflammatory response in CNV lesions were analyzed. Results: We showed that ten days of the CSF1R inhibitor PLX3397 treatment followed by 11 days of drug withdrawal was sufficient to stimulate rapid repopulation of the retina with new microglia. Microglial repopulation attenuated pathological choroid neovascularization and dampened cellular senescence in CNV lesions. Repopulating microglia exhibited lower levels of activation markers, enhanced phagocytic function and produced fewer cytokines involved in the immune response, thereby ameliorating leukocyte infiltration and attenuating the inflammatory response in CNV lesions. Discussion: The microglial repopulation described herein are therefore a promising strategy for restricting inflammation and choroidal neovascularization, which are important players in the pathophysiology of AMD.

Efficacy and safety of sympathetic radiofrequency thermocoagulation in the treatment of cold hypersensitivity.

Background: Cold hypersensitivity (CH) is a sensation of cold in the limbs and (or) body of a patient in an environment that is not considered cold by unaffected people, or a strong feeling of cold at a relatively low temperature. However, the currently available treatments are limited and often unsatisfactory. This study aimed to evaluate the clinical efficacy and safety of the sympathetic radiofrequency thermocoagulation (RF-TC) technique in patients with CH disorder. Methods: The study is a retrospective analysis. A total of 71 were entered into the final analysis and all patients underwent computed tomography-guided thoracic (lumbar) sympathetic nerve RF-TC on an elective basis. The values of terminal temperature (T) and perfusion index (PI) of patients before and after treatment were recorded. Patients were followed up clinically at regular intervals and their Visual Analog Scale (VAS) and Pittsburgh Sleep Quality Index (PSQI) scores were recorded to detect postoperative complications and assess patient satisfaction with the treatment. Results: All patients completed the radiofrequency treatment. Compared with the preoperative period, VAS and PSQI scores were significantly lower at all postoperative time periods (P < 0.001). Patients had significantly higher postoperative terminal temperatures and perfusion indices on the right and left sides than before surgery (P < 0.001). The overall patient satisfaction score was 4 (3-5) at 3 years of postoperative follow-up. There were 20 recurrences (28.2%). The main postoperative complications were postoperative local pain and compensatory hyperhidrosis. No other adverse events or deaths were observed. Conclusion: RF-TC for CH could be a feasible, effective, and safe treatment option to improve patients' symptoms of cold sensation. Yet, more researches are needed to verify this potentially efficient and standardized treatment.