MiR-452-5p facilitates retinoblastoma cell growth and invasion via the SOCS3/JAK2/STAT3 pathway.

Retinoblastoma (RB) is an intraocular tumor in children. Accumulated evidence confirms that microRNAs (miRNAs) exert critical functions in RB. This research aimed to investigate the miR-452-5p function in RB. MiR-452-5p expressions in RB were tested with quantitative real-time polymerase chain reaction (PCR). MiR-452-5p functions in RB were evaluated via Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, Western blot, and Transwell. MiR-452-5p mechanism in RB was assessed using bioinformatics software Starbase and dual-luciferase reporter gene assay. Meanwhile, miR-452-5p function in RB in vivo was examined by constructing tumor xenografts in nude mice, immunohistochemistry, and Western blot assays. MiR-452-5p was overexpressed in RB tissues and cells, and miR-452-5p expression was positively correlated with RB clinicopathology including the Largest tumor base (mm) and Differentiation. Functionally, miR-452-5p knockdown restrained RB cell proliferation, invasion, epithelial-mesenchymal transition (EMT), and facilitated cell apoptosis. Mechanistically, suppressors of cytokine signaling (SOCS3) knockdown restored the inhibitory effects of miR-452-5p knockdown on RB cells. Meanwhile, in vivo studies further corroborated that miR-452-5p knockdown reduced RB tumor growth, EMT, and accelerated apoptosis in vivo. Also, miR-452-5p knockdown increased SOCS3 protein levels, and decreased phosphorylated Janus kinase 2/Janus kinase 2 (JAK2), phosphorylated signal transducer and activator of transcription 3/signal transducer and activator of transcription 3 (STAT3) in vivo. MiR-452-5p accelerated RB cell growth and invasion by SOCS3/JAK2/STAT3.

Cold protection allows local cryotherapy in a clinical-relevant model of traumatic optic neuropathy.

Therapeutic hypothermia (TH) is potentially an important therapy for central nervous system (CNS) trauma. However, its clinical application remains controversial, hampered by two major factors: (1) Many of the CNS injury sites, such as the optic nerve (ON), are deeply buried, preventing access for local TH. The alternative is to apply TH systemically, which significantly limits the applicable temperature range. (2) Even with possible access for 'local refrigeration', cold-induced cellular damage offsets the benefit of TH. Here we present a clinically translatable model of traumatic optic neuropathy (TON) by applying clinical trans-nasal endoscopic surgery to goats and non-human primates. This model faithfully recapitulates clinical features of TON such as the injury site (pre-chiasmatic ON), the spatiotemporal pattern of neural degeneration, and the accessibility of local treatments with large operating space. We also developed a computer program to simplify the endoscopic procedure and expand this model to other large animal species. Moreover, applying a cold-protective treatment, inspired by our previous hibernation research, enables us to deliver deep hypothermia (4 °C) locally to mitigate inflammation and metabolic stress (indicated by the transcriptomic changes after injury) without cold-induced cellular damage, and confers prominent neuroprotection both structurally and functionally. Intriguingly, neither treatment alone was effective, demonstrating that in situ deep hypothermia combined with cold protection constitutes a breakthrough for TH as a therapy for TON and other CNS traumas.

Hypothermic therapy is a radical type of treatment that involves cooling a person's core body temperature several degrees below normal to protect against brain damage. Lowering body temperature slows blood flow, which reduces inflammation, and eases metabolic demands, similar to hibernation. It can also reduce lasting damage to the brain and aid recovery when used to treat people who have gone into cardiac arrest, where their heart suddenly stops beating. Recently, there has been renewed interest in using hypothermic therapy to treat people who have sustained traumatic brain injuries, which can cause brain swelling, and other nerve injuries. However, its use remains controversial because clinical trials have failed to show that inducing mild hypothermia provides any benefit for people with severe nerve injuries. This might be because cooling cells to near-freezing temperatures can damage their internal structural supports, called microtubules, thwarting any therapeutic benefit. Traumatic optical neuropathy is a type of injury in which the optic nerve ­ the nerve that connects the eyes to the brain ­ is damaged or severed, causing vision loss. There is currently no clinically proven treatment for this condition, nor is there a system that can test local treatments in large animals as a prior test to using the treatment in the clinic. Therefore, Zhang et al. wanted to establish such a animal model and test whether local hypothermic therapy could help protect the optic nerve. Zhang et al. used a surgical tool guided by an endoscope (a thin plastic tube with a light and camera attached to it) to injure the optic nerves of goats, and then deliver hypothermic therapy. To cool the surgically-injured nerves to a chilly 4C, Zhang et al. applied a deep-cooling agent, using a second reagent (a cocktail of protease inhibitors) to protect the cells' microtubules from cold-induced damage, an insight gained from a previous study of hibernating animals. This was critical, as the hypothermic therapy was only effective when the secondary protective agent was applied. The combination therapy developed by Zhang et al. relieved some aspects of nerve degeneration at the injury site and activated an anti-inflammatory response in cells, but did not restore vision. To simplify surgical techniques, Zhang et al. also developed a computer program which generates virtual surgical paths for up-the-nose endoscopic procedures based on brain scans of an animal's skull. This program was successfully applied in a range of large animals, including goats and macaque monkeys. Zhang et al.'s work establishes a method to study treatments for traumatic optical neuropathy using large animals, including hypothermic therapy. The methods developed could also be useful to study other optic nerve disorders, such as optic neuritis or ischemic optic neuropathy.

Immediate Endoscopic Dacryocystorhinostomy in Patients With New Onset Acute Dacryocystitis.

OBJECTIVES: To compare the results of immediate endoscopic dacryocystorhinostomy (En-DCR) and delayed En-DCR in the treatment of new-onset acute dacryocystitis (AD). STUDY DESIGN: This report describes a prospective randomized controlled interventional case series. METHODS: Between April 2009 and May 2019, 176 adults presenting at a tertiary eye care center with new-onset AD manifesting within the last 48 hours were randomized into two groups. Altogether, 160 patients (48 male, 112 female) were included in this study, with a median age of 52.8 years (range: 18-82). Patients in group A underwent urgent En-DCR, although those in group B underwent a delayed En-DCR after 2 to 5 days of systematic antibiotic treatment. Variables compared between these two groups included the time for resolution of acute external inflammation, free lacrimal passage reconstruction (LPR) success rates, and complication rates. RESULTS: Postoperative data were collected from 86 patients in group A and 74 patients in group B. Patients that underwent immediate En-DCR exhibited a quicker resolution of acute inflammation (P < .05). Patients that underwent delayed surgery experienced compilations of acute inflammation, with 10 ultimately developing skin fistulization and 4 exhibiting orbital cellulitis before surgery. The success rate of LPR at 12 months after surgery was higher in group A (81/86 94.2%) relative to group B (62/74 83.8%; P < .05). CONCLUSIONS: Immediate En-DCR is associated with quicker disease resolution and a higher long-term success rate, although reducing the incidence of complications including skin fistulization and the spread of infection. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:278-283, 2022.

In vivo evaluation of outer retinal function and structure after retrobulbar optic nerve crush by lateral orbitotomy in goats.

Large animal model of optic nerve crush (ONC) plays an important role in translating novel therapeutic strategies developed in rodent model to clinical application. Due to the poor accessibility of the optic nerve (ON) in humans and large animals, lateral orbitotomy is needed to expose the retrobulbar ON. This study was to explore the effects of ONC and ON exposure with lateral orbitotomy (sham surgery) on the outer retinal function and structure in goats by using standard flash electroretinogram (FERG) and spectral-domain optical coherence tomography (SD-OCT). We found that ONC led to a transient reduction in FERG amplitudes at 1 week post injury (wpi), which recovered gradually over 2 months afterwards. Sham surgery alone also caused a similar pattern of amplitude reduction in FERG, although not as significantly as ONC did. Transient outer retinal thickening following ONC occurred at 4 wpi (when progressive thinning of the ganglion cell complex began), peaked at 8 wpi, then recovered gradually at 12 wpi. In contrast, outer retinal thickness remained unchanged statistically 3 months after sham surgery. Fundus fluorescein angiography showed that neither ONC nor ON exposure with lateral orbitotomy significantly caused any significant delay or absence of central retinal vascular filling. In summary, ONC with lateral orbitotomy affects outer retinal function and structure transiently.

Orbital Infection Due to Medial Wall Fracture: Three Cases of Orbital Complications Caused by Paranasal Sinusitis Secondary to Medial Orbital Wall Fracture.

PURPOSE: The aim of this study was to report 3 cases of orbital complications in patients with secondary sinusitis due to medial orbital wall fracture. We believe that sinusitis can be secondary to the fracture of the medial orbital wall when the sinus drainage orifice is blocked due to some fracture pieces or other blocking factors. We precisely show the direct evidence of the blocking factors through radiology. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: All patients had intraorbital complications and a history of traumatic orbital medial fracture as well as imaging findings of sinusitis. METHODS: A medical record review of clinical history, imaging studies, and surgical and treatment outcomes were performed. MAIN OUTCOME MEASURES: Postoperative visual acuity, appearance, eye movement, surgical and imaging findings. RESULTS: Three patients (2 males and 1 female; average age 38.33 years [range, 11-65]) received endoscopic surgery for orbital complications related to sinusitis. All patients had evidence of paranasal sinusitis after the orbital injury. Two patients were treated with antibiotics before the operation, but there was no significant improvement. All patients underwent transnasal endoscopic sinotomy. Two patients received orbital abscess incision and drainage surgery and 1 patient underwent a cyst excision operation. The visual acuity of the 3 patients was improved after the operation, and the clinical examination was significantly improved. CONCLUSIONS: The anatomy of the orbit is closely related to the nasal cavity. The fracture of the medial orbital wall often causes abnormal anatomy of the sinus outflow tract. For the 3 of our patients, the blocking factors of sinus orifices were fracture fragment, orbital bone deformation, and the formation of giant nasal intraorbital mucocele. Sinusitis possibly occurs when drainage is not smooth. Infections develop due to the secretions retaining and accumulation of microorganisms. Inflammation from the sinus can be spread into the orbit in various ways. Our 3 patients indicate that a fracture of the inner orbital wall may cause sinusitis. When the patient is injured again or sneezing or in other conditions when the pressure in the nasal cavity increases, inflammation of the sinuses enters the orbit, causing serious intraorbital complications. It is necessary to carefully follow-up on the medical history, combined with imaging examination, to prevent the misdiagnosis of intraorbital hemorrhage or hematoma from affecting the treatment.In recent years, more and more cases of intraorbital complications caused by sinusitis have been reported.1,2 Severe intraorbital inflammation can pose a threat to vision and even life. With the great tool of the endoscope, nasal-orbital problems can be well solved. For our 3 patients, we opened the paranasal sinus and removed the occlusion of the sinus orifice through transnasal endoscopy. All patients achieved good surgical and clinical results.