Rutin promotes M2 phenotype microglia polarization by suppressing the JAK/STAT3 signaling to protect against retinal ischemia-reperfusion injury.

We aimed to investigate the neuroprotective effect of rutin on retinal ganglion cells (RGCs) under ischemia-reperfusion (I/R) conditions and the underlying mechanisms involving microglia polarization and JAK/STAT3 signaling. RGCs isolated from C57/Bl6 mice were co-cultured with BV2 microglial cells under normal or in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) conditions. Rutin's effects were evaluated by assessing cell viability, apoptosis rates, cytokine levels, microglial polarization markers and JAK/STAT3 phosphorylation levels. The specific target is confirmed through the inhibitory effect of rutin on the respectively activated signaling factors. Furthermore, molecular docking analyses elucidated rutin-JAK1 interactions. OGD/R conditions significantly reduced RGC viability, exacerbated by BV2 co-culture. However, both 1 µM and 5 µM rutin treatment dose-dependently enhanced RGC viability, reduced apoptosis, and suppressed pro-inflammatory cytokine levels. Western blot analysis indicated that rutin promoted the M2 microglial phenotype and suppressed JAK/STAT3 signaling. Notably, rutin selectively inhibited JAK1 phosphorylation without affecting STAT3. Molecular docking highlighted potential interaction sites between rutin and specific JAK1 pseudokinase domain. Rutin exerts neuroprotective effects against retinal I/R injury by promoting M2 microglial polarization, potentially through the selective inhibition of JAK1 phosphorylation within the JAK/STAT3 signaling pathway. These findings provide a foundation for the therapeutic potential of rutin in retinal I/R injuries.

Five-in-one: a novel, cost-effective yet simple use of micro needle holder.

AIM: To achieve a balance between efficiency and cost in the management of medical instrument by the use of micro needle holder. METHODS: In this study, the novel multifunctional use of micro needle holders was performed between 2018 and 2019 at the Department of Ophthalmology in the 4 hospitals in Shaanxi Province. In this innovation, the micro needle holders were initially used as micro forceps to remove sutures, as eye spud to safety extract foreign body from cornea, as ciliary forceps to remove trichiasis, as well as punctal dilator to dilate most small puncta. RESULTS: Using this technique, the medical costs of both procurement and sterilization were cut off in the selected 4 hospitals. The purchase cost has dropped by roughly 50%. The sterilization cost was decreased by about 30%. CONCLUSION: The innovation in the five-in-one multifunctional use of micro needle holders saves the medical costs.

Is there a primitive reflex residue underlying Marcus Gunn Syndrome? Rat electrophysiology.

AIM: To make an electrophysiological demonstration of a possible jaw muscle afferents-oculomotor neural pathway that was proposed by our previous works on rats, which substantiates an early "release hypothesis" on pathogenesis of human Marcus Gunn Syndrome (MGS). METHODS: Extracellular unit discharge recording was applied and both orthodromic and spontaneous unitary firing were recorded in the oculomotor nucleus (III), and the complex of pre-oculomotor interstitial nucleus of Cajal and Darkschewitsch nucleus (INC/DN), following electric stimulation of the ipsilateral masseter nerve (MN) in rats. RESULTS: Extracellular orthodromic unit discharges, with latencies of 3.7±1.3 and 4.7±2.9ms, were recorded unilaterally in the III, and the INC/DN neurons, respectively. Spontaneous unit discharges were also recorded mostly in the INC/DN and less frequently in the III. Train stimulation could prompt either facilitation or inhibition on those spontaneous unit discharges. The inhibition pattern of train stimulation on the spontaneous discharging was rather different in the III and INC/DN. A slow inhibitory pattern in which spontaneous firing rate decreased further and further following repeated train stimulation was observed in the III. While, some high spontaneous firing rate units, responding promptly to the train stimuli with a short-term inhibition and recovered quickly when stimuli are off, were recorded in the INC/DN. However, orthodromic unit discharge was not recorded in the III and INC/DN in a considerable number of experiment animals. CONCLUSION: A residual neuronal circuit might exist in mammals for the primitive jaw-eyelid reflex observed in amphibians, which might not be well-developed in all experimental mammals in current study. Nonetheless, this pathway can be still considered as a neuroanatomic substrate for development of MGS in some cases among all MGS with different kind of etiology.

Is Marcus Gunn jaw winking a primitive reflex? Rat neuroanatomy.

AIM: To investigate a possible trigeminal proprioceptive-oculomotor neural pathway and explore possible synaptic connections between neurons in this pathway. Attempt to bring a new insight to mechanism of Marcus Gunn syndrome (MGS). METHODS: Anterograde and retrograde tract tracing was applied and combined with immunofluorescent stain in rats. After electrophysiological identifying mesencephalic trigeminal nucleus (Vme) neurons, intracellular injection of tracer was performed to trace axon trajectory. RESULTS: Following injections of anterograde tracers into the Vme, labeled terminals were observed ipsilateral in oculomotor and trochlear nuclei (III/IV), as well as in their premotor neurons in interstitial nucleus of Cajal and Darkschewitsch nucleus (INC/DN). Combining with choline acetyltransferase (ChAT) immunofluorescent stain, it showed that Vme projecting terminals contact upon ChAT positive III/IV motoneurons under confocal microscope. By retrograde labeling premotor neurons of the III, it showed that Vme neuronal terminals contact with retrogradely labeled pre-oculomotor neurons in the INC/DN. Axons of intracellularly labeled Vme neurons that respond to electric stimuli of the masseter nerve traveled into the ipsilateral III. CONCLUSION: There may exist a trigeminal proprioceptive-oculomotor system neural circuit in the rat, which is probably related to vertical-torsional eye movements. Possible association of this pathway with MGS etiology was discussed.

Uveal effusion following acute primary angle-closure: a retrospective case series.

AIM: To evaluate the morphological changes in anterior segment in Chinese patients with uveal effusion (UE) after the attack of acute primary angle-closure (APAC) using ultrasound biomicroscopy (UBM), and to assess the clinical course and prognosis of the disease. METHODS: In a retrospective case series, 26 eyes in 26 consecutive patients diagnosed with UE after the treatment of intraocular pressure (IOP)-lowering medication for the attack of APAC were enrolled. The unaffected fellow eyes served as controls. The morphological changes were observed by ultrasonography, slit lamp microscopy and gonioscopy. UBM was used to assess the degree and extent of effusion based on the analysis of parameters associated with UE. RESULTS: The mean IOP was 9.2 (SD 2.1) mm Hg at the diagnosis of UE after IOP-lowering medication, while 14.1 (SD, 2.6) mm Hg in the fellow eyes (P=0.000). The anterior chamber depth (ACD) (P=0.000), angle opening distance at 500 µm (AOD500) (P<0.01) and anterior chamber angle (ACA) (P<0.05) were decreased significantly, while ciliary body thickness (CBT) (P<0.05) increased significantly in UE eyes. UE grade analysis showed 7 eyes in grade 1, 9 eyes in grade 2, and 10 eyes in grade 3. Quadrant scores were performed of 4 eyes in 1 quadrant, 3 eyes in 3 quadrants, and 19 eyes in 4 quadrants. There was the positive correlation between grade and quadrant score (r=0.644, P=0.000). The effusion on all eyes were recovered after medication, which mean IOP was 13.9 (SD, 2.8) mm Hg. CONCLUSION: UE is a frequent complication in Chinese patients after the attack of APAC, partially associated with hypotony. The severity of UE is correlation with height of effusion, extent of detachment, and shallower ACD.