The objective of the study was to evaluate the amended International Classification of Headache Disorders (third edition, beta version, ICHD-3 beta) with a retrospective analysis. A total of 22 patients diagnosed with painful ophthalmoplegia and Tolosa-Hunt syndrome (THS) in our hospital were retrospectively studied. The following clinical data were collected: symptoms, signs, location of inflammatory tissue, time interval of paresis following the onset of pain, pain and signs of resolution, follow-up and relapse. Pain and diplopia were found in 22 (100 %) and 20 cases (91 %). The sympathetic nerve was involved in 6 cases (27 %). Paresis followed the pain for an average of 8 ± 5.87 days. Serial magnetic resonance imaging (MRI) revealed granulomatous lesion that was visible in 20 patients (91 %). 19 patients (86 %) demonstrated the lesions located in the cavernous sinus, orbital apex or superior orbital fissure. One lesion extended to the intracranial structure. Pain was relieved in 20 cases (91 %) within 72 h and no patient had complete relief from paresis. According to our study, we think the time course of relief should be undefined. Headache location is hard to describe accurately. Normal MRI should be involved in THS diagnoses. The lesion of THS can extend beyond the cavernous sinus and the orbit. The time interval between headache and paresis can exceed 2 weeks.

Corneal chemical burns are common ophthalmic injuries that may result in permanent visual impairment. Although significant advances have been achieved on the treatment of such cases, the structural and functional restoration of a chemical burn-injured cornea remains challenging. The applications of polysaccharide hydrogel and subconjunctival injection of mesenchymal stem cells (MSCs) have been reported to promote the healing of corneal wounds. In this study, polysaccharide was extracted from Hardy Orchid and mesenchymal stem cells (MSCs) were derived from Sprague-Dawley rats. Supplementation of the polysaccharide significantly enhanced the migration rate of primarily cultured rat corneal epithelial cells. We examined the therapeutic effects of polysaccharide in conjunction with MSCs application on the healing of corneal alkali burns in rats. Compared with either treatment alone, the combination strategy resulted in significantly better recovery of corneal epithelium and reduction in inflammation, neovascularization and opacity of healed cornea. Polysaccharide and MSCs acted additively to increase the expression of anti-inflammatory cytokine (TGF-β), antiangiogenic cytokine (TSP-1) and decrease those promoting inflammation (TNF-α), chemotaxis (MIP-1α and MCP-1) and angiogenesis (VEGF and MMP-2). This study provided evidence that Hardy Orchid derived polysaccharide and MSCs are safe and effective treatments for corneal alkali burns and that their benefits are additive when used in combination. We concluded that combination therapy with polysaccharide and MSCs is a promising clinical treatment for corneal alkali burns and may be applicable for other types of corneal disorder.

This study aims to explore the effects of exosomes, secreted by retinal pigment epithelial (RPE) cells under oxidative stress (OS), on apoptosis and inflammation of normal RPE cells. Exosomes secreted by normal RPE cells (named as exo) and rotenone (2.5 µmol/L) stimulated RPE cells (named as rot-exo) were isolated and extracted by multi-step differential centrifugation for morphology observation under a transmission electron microscopy. pcDNA3.1a, pcDNA3.1a-Apaf1, and p3xFlag-CMV-caspase-9 plasmids were constructed and transfected into ARPE-19 cells. Exosomes secreted by ARPE-19 cells were injected into the vitreous body of rats to verify the effect of Apaf1 and caspase-9 on cell apoptosis and inflammation. Co-immunoprecipitation was applied to clarify the interaction of Apaf1 with caspase-9. Exosomes secreted by rotenone stimulated ARPE-19 cells could induce cell apoptosis, oxidative injury, and inflammation in ARPE-19 cells. Exosomes secreted under OS can damage retinal functions of rats and have upregulated expression of Apaf1. Overexpression of Apaf1 in exosomes secreted under OS can cause the inhibition of cell proliferation, the increase of cell apoptosis and elicitation of inflammatory response in ARPE-19 cells. Exosomes derived from ARPE-19 cells under OS regulate Apaf1 expression to increase cell apoptosis and to induce oxidative injury and inflammatory response through a caspase-9 apoptotic pathway. K E Y W O R D S caspase-9, cell apoptosis, exosomes, reactive oxygen species, retinal pigment epithelium cells 1 | INTRODUCTION Retinal pigment epithelium (RPE) is a monolayer of cells that undertake the function and viability of photoreceptor cells. 1 RPE could provide nutrients to secure visual function and could impact the formation of the outer blood-retinal barrier which avoids nonspecific diffusion and material transportation from the choroid. 2 The degradation of RPE cells is part of the pathology involved in age-related macular degeneration (AMD) whose etiology remains to be largely determined. 3 RPE is vulnerable to oxidative stress (OS), particularly to reactive oxygen species (ROS). 4 OS is Yifeng Ke and Xiaoe Fan contributed equally to this work.

Background: Numerous metabolic parameters can be changed during hemodialysis in the end-stage renal disease (ESRD) caused by systemic diseases, such as diabetes mellitus, hypertension. Some ocular parameters also can be variable due to the changes after hemodialysis. This study evaluates the effects of ocular parameters, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), retinal arteriolar caliber (RAC), retinal venular calibre (RVC), in ESRD patients following hemodialysis. Materials and methods: Two-hundred and two ESRD patients were recruited resulting in 404 eyes evaluations. All patients underwent hemodialysis in the Dialysis Unit of the Second Hospital of Tianjin Medical University. BCVA, CMT, IOP, SFCT, RAC and RVC were evaluated before and after hemodialysis. Systemic parameters were collected such as age, body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), duration of hemodialysis, body weight changes, high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), very low density lipoprotein cholesterol (VLDLC), glycosylated hemoglobin (HbA1c). Results: The causes of ESRD patients included chronic glomerulonephritis ( n = 65), diabetes mellitus ( n = 60), hypertensive nephrosclerosis ( n = 37), and other causes ( n = 40). In our study, BCVA ( p = .817), CMT ( p = .252) and IOP ( p = .978) did not significantly change after hemodialysis. SFCT significantly decreased from 254.29 ± 69.36 μm to 235.54 ± 659.90 μm ( p = .002) following hemodialysis. SFCT changes were significantly correlated with SBP ( p = .042) and body weight changes ( p = .044). The RAC and RVC were dilated significantly ( p = .033, p = .007). RVC changes were correlated with baseline DBP ( p = .003), HDLC ( p = .009), LDLC ( p = .004) and changes in DBP ( p = .037) and body weight ( p = .001). Conclusion: Hemodialysis can affect various ocular parameters including SFCT, RAC and RVC, which changed significantly following hemodialysis. Whereas BCVA, IOP and CMT did not change after hemodialysis in ESRD patients. The systemic compensatory mechanisms of the changes in SBP, DBP, body weight following hemodialysis need further study.

Objective Retinal degenerative diseases remain the dominant causes of blindness worldwide, and cell replacement is viewed as a promising therapeutic direction. However, the resources of seed cells are hard to obtain. To further explore this therapeutic approach, human embryonic stem extracellular vesicles (hESEVs) were extracted from human embryonic stem cells (hESCs) to inspect its effect and the possible mechanism on retinal Müller cells and retinal function. Methods hESEVs were extracted by multi-step differential centrifugation, whose morphologies and specific biomarkers (TSG101, CD9, CD63, and CD81) were observed and measured. After hESEVs were injected into the vitreous cavity of RCS rats, the retinal tissues and retinal functions of rats were assessed. The alteration of Müller cells and retinal progenitor cells was also recorded. Microvesicles (MVs) or exosomes (EXOs) were extracted from hESCs transfected with sh-HSP90 or pcDNA3.1-HSP9, and then incubated with Müller cells to measure the uptake of EVs, MVs, or EXOs in Müller cells by immunofluorescence. The retrodifferentiation of Müller cells was determined by measuring Vimentin and CHX10. qRT-PCR and western blot were used to detect HSP90 expression in MVs and evaluate Oct4 level in Müller cells, and Co-IP to inspect the interaction of HSP90 and Oct4. Results RCS rats at the postnatal 30 days had increased retinal progenitor cells which were dedifferentiated from Müller cells. hESEVs were successfully extracted from hESCs, evidenced by morphology observation and positive expressions of specific biomarkers (TSG101, CD9, CD63, and CD81). hESEVs promoted Müller cells dedifferentiated and retrodifferentiated into retinal progenitor cells evidenced by the existence of a large amount of CHX10-positive cells in the retinal inner layer of RCS rats in response to hESEV injection. The promotive role of hESEVs was exerted by MVs demonstrated by elevated fluorescence intensity of CHX10 and suppressed Vimentin fluorescence intensity in MVs rather than in EXOs. HSP90 in MVs inhibited the retrodifferentiation of Müller cells and suppressed the expression level of Oct4 in Müller cells. Co-IP revealed that HSP90 can target Oct4 in Müller cells. Conclusion hESEVs could promote the retrodifferentiation of Müller cells into retinal progenitor cells by regulating the expression of Oct4 in Müller cells by HSP90 mediation in MVs.