Non-steroidal anti-inflammatory drugs in postoperative hand fracture management:Do they positively or negatively impact recovery?

This editorial explores the impact of non-steroidal anti-inflammatory drugs(NSAIDs)on postoperative recovery in hand fracture patients,amidst shifting pain management strategies away from opioids due to their adverse effects.With hand fractures being significantly common and postoperative pain management crucial for recovery,the potential of NSAIDs offers a non-addictive pain control alternative.However,the controversy over NSAIDs'effects on bone healing—stemming from their Cyclooxygenase-2 inhibition and associated risks of fracture non-union or delayed union—necessitates further investigation.Despite a comprehensive literature search,the study finds a lack of specific research on NSAIDs in postoperative hand fracture management,highlighting an urgent need for future studies to balance their benefits against possible risks.

Processus pour le développement d’une stratégie d’évaluation de la qualitéde vie en cancer avancépédiatrique Process for Developing a Quality of Life Assessment Strategy in Advanced Pediatric Cancer

In pediatric advanced cancer,i.e.,when cancer-targeted treatments are not effective,care provided to patients is of palliative nature.It aims at limiting symptoms and optimizing quality of life(QoL).To orient care,it is necessary to know and measure what is really important for young people.Unfortunately,tools are still scarce in this context.The aim of this paper is to describe the development process of a new QoL assessment method,the Advance QoL program.This is specifically designed for the clinical context of pediatric advanced cancer.Three previous studies carried out by our team identified seven important QoL domains for this population.We developed a tool named Advance QoL—parent/caregiver version.A current study aims to develop self-reported versions of the Advance QoL for children(8-12 years)and adolescents(13-18 years)with advanced cancer.In the very near future,the Advance QoL tool will be available in three versions(parents/caregivers,children,and adolescents)ready to be tested in validation studies.Regular assessment of the QoL of young people with cancer is a central process in defining targets for care and should be carried out throughout the trajectory,including when cancer is at an advanced stage,i.e.,when no standard treatment options are available.

From cortex to cord: motor circuit plasticity after spinal cord injury

Spinal cord injury is associated with chronic sensorimotor deficits due to the interruption of ascending and descending tracts between the brain and spinal cord. Functional recovery after anatomically complete spinal cord injury is limited due to the lack of long-distance axonal regeneration of severed fibers in the adult central nervous system. Most spinal cord injuries in humans, however, are anatomically incomplete. Although restorative treatment options for spinal cord injury remain currently limited, research from experimental models of spinal cord injury have revealed a tremendous capability for both spontaneous and treatment-induced plasticity of the corticospinal system that supports functional recovery. We review recent advances in the understanding of corticospinal circuit plasticity after spinal cord injury and concentrate mainly on the hindlimb motor cortex, its corticospinal projections, and the role of spinal mechanisms that support locomotor recovery. First, we discuss plasticity that occurs at the level of motor cortex and the reorganization of cortical movement representations. Next, we explore downstream plasticity in corticospinal projections. We then review the role of spinal mechanisms in locomotor recovery. We conclude with a perspective on harnessing neuroplasticity with therapeutic interventions to promote functional recovery.

Modification of Nano Tourmaline Surface Treatment Agent and Its Performance on Negative Ion Release

In this paper,a kind of wall fabric’s surface treatment agent modified with nonionic surfactant was reported.This surface treatment agent was prepared by using nano tourmaline powder dispersion in water with surfactant as dispersants by sand milling.Under the influence of different dispersants,the negative ions releasing amount of functional wall fabrics,the milling process and the storage stability of nano tourmaline powder dispersion were discussed.The results showed that nano tourmaline powder dispersion achieved the smallest average diameter of 44 nm and had best storage stability that the average diameter maintained below 200 nm in 17 days when the addition amount of dispersant was 20 percent of the tourmaline powders’weight.What is more,the quantity of negative ion releasing achieved 6500 ion/cm3 when addition amount of dispersant was 30 percent.This technique could be used to strengthen productivity of nano tourmaline powder dispersion.

Targeting the motor cortex to restore walking after incomplete spinal cord injury

Spinal cord injury(SCI),second only to stroke,is the leading cause of paralysis.The ability to walk is often lost after SCI,reducing independence and quality of life.Restoration of walking is cited as a priority among persons with SCI of all degrees of severity,chronicity,or age at injury.As 70%of SCIs are anatomically incomplete,some neural connections relaying information to and from the brain are spared.

Learning and competence development via clinical cases-what elements should be investigated to best train good medical doctors?

In European higher education,application of information technology,concentration on the learning-processes,consistent implementation,transfer learning,case-based learning,autonomous learning has been extensively studied in the last decade.Educational sciences based on neuroscientific findings use brain-based learning and teaching,including integrated thematic instructions and emotion-theory.Elements essential to this strategy,such as theory and methods for learning,competencies,attitudes,social reality,and a metadiscourse are described herein.Research on learning tends to focus on declarative knowledge,associative learning with conditional stimuli,and procedural knowledge with polythematic/crosslinking thinking.Research on competencies:In research on competencies(e.g.,for clinical reasoning,decision-making),intuitive and analytical components are studied.As repeated presentation and exercising of clinical cases is crucial for an efficient learning process,the implementation of interactive scenarios including affectively involving didactics is considered.For competence-development observational methods,questionnaires/item sets or factors have to be targeted and empirically validated.Attitudes and social reality:Clinical decision-making,identification processes and attitudes(“Hidden curriculum”),as well as secondary socialization processes(integration of social norms,values,preparation of role-acquisition,occupational role)are studied via process research,conceptual research,and observational methods.With respect to social reality research,conscious and unconscious bargaining processes have to be taken into account.Methodology:Neuroscience-memory,neuronal,molecular biology,and computer science(Neurocircuits)are integrated into observational process research(e.g.,affective-cognitive interface,identification processes)and conceptual research is added and studied on the meta-level,including discussion of research paradigms.This discussion provides ongoing feedback to projects in a hermeneutic circle.

High-Fat Diets-Induced Metabolic Alterations Alter the Differentiation Potential of Adipose Tissue-Derived Stem Cells

Background: Adipose tissue-derived stem cells (ASC) possess the ability to differentiate into adipocytes or endothelial cells to help in the adipogenesis, vasculogenesis and vascular repair. This study aims at determining the impact of high-fat diets (HFD)-induced type 2 diabetes (T2D) on the differentiation potential of ASC. Results: C57BL/6J male mice were fed a vegetal (VD) or an animal (AD) HFD. Isolation of ACS from mice showing different levels of metabolic alterations reveals that advanced T2D did not affect the number of cells per gram of tissue. Rather, a higher proportion of inflammatory CD36+ cells was identified in HFD fed mice. Despite a marked decreased expression of adipogenic genes (aP2, C/EBPα and PPARγ2), ASC from HFD groups had a higher adipogenic potential and a lower endothelial differentiation potential in vitro compared to control. ASC from the VD group had enhanced cyclin B1 expression and had more adipogenic potential compared to AD group. Conclusion: Our results demonstrate that the metabolic modifications, linked to the nature of fatty acids in diets, modulate the differentiation potential of ASC with increased adipogenesis to the detriment of the endothelial pathway. Results highlight the importance of evaluating the ASC differentiation behavior in a context of autologous cell-based therapy for the repair of vascular tissues in diabetic patients.

Affect regulation in psychoanalytic treatments of patients with a borderline personality disorder–psychoanalysis and psychodynamic psychotherapy–a comparison

BACKGROUND A recent meta-analysis has confirmed that the effects of psychotherapy on patients with borderline personality disorders(BPD)are still insufficiently understood.Evidence of differences between different types of therapies has been questioned.AIM To study repetitive interaction patterns in patients with BPD undergoing either psychoanalysis or psychodynamic therapy.METHODS Psychoanalysis(PSA)or psychodynamic psychotherapy(PDT)was administered to 10 patients each,the two groups were matched.Therapy regimens were applied according to care as usual/manualized including quality control and supervision as usual.Randomization to one of the groups was done after baseline assessment.During classical PSA(n=10)and PDT(n=10),semiannually,recordings(audio or video)of five consecutive therapy sessions were taken over three years for an ex-post analysis.The patients'characteristics,such as affect parameters[Affect regulation and experience Q-sort(AREQ)],quality of object relations(quality of object relations scale)and personality traits[Shedler-Westen Assessment Procedure(SWAP-200)]were analyzed retrospectively by independent raters.Therapeutic action(psychotherapy process Q-sort)and affective(re)actions of the patients(AREQ)were then analyzed in relation to changes found in the patients'characteristics.RESULTS During the first year of therapy(PSA:n=10;PDT:n=9),the therapeutic method PSA was associated with significant improvements in the variable"SWAP Borderline",while in PDT change was not significantly different to baseline(PSA:P=0.04;PDT:P=0.33).Long-term results and follow up was available for seven participants in PSA and for five in PDT after three years;change in SWAP borderline for the whole sample was not significant at this time point when confronting to baseline(P=0.545).However,differences between PSA and PDT were significant when analyzing the“mean change”in the SWAP Borderline variable after one year of therapy(P=0.024):PSA led to slightly increased BPD symptoms,while PDT to a decrease;for the long run,variance of observed change was higher in PSA than in PDT(SDPSA±9.29 vs SDPDT±7.94).Our assumption that transference interpretations,closely followed by affective changes in the patient,could be useful modes of interaction was reproducible in our findings,especially when looking at the descriptive findings in the long-term data.The analysis of repetitive interaction structures demonstrated a very specific"time-lag"between therapeutic intervention and a corresponding increase in positive affect in successful therapy cases.CONCLUSION Exploring the change processes in the patients'characteristics and linking these changes to specific treatment strategies is of clinical importance when starting treatment and for its long-term progress.

From Research Data to Intervention Models: Intervening with All Stakeholders

[French version]En tant que dispositif de recherche innovant pour développer et mettre en oeuvre les préventions,la recherche interventionnelle en santédes populations(RISP)occupe une place particulière dans le déploiement de la stratégie décennale française de lutte contre les cancers.

AB061. Changes in eye movement strategies during a discrimination task in the presence of artificial central scotomas

Background:The goal of the present research was to study whether the presence of an artificial central scotoma resulted in changes in eye movement strategies over the course of multiple days of training.We wished to determine how central vision loss,similar to age macular degeneration(AMD),affects eye movements,specifically the foveal-target alignment.We also wished to determine if an invisible compared to a visible scotoma led to delayed or different strategies,given that AMD patients are mostly unaware of their condition as they are unconscious of the presence of their central scotoma.Methods:Eleven healthy participants(6 females,M=22.18,SD=1.94)were asked to perform a discrimination task,where they responded whether the orientation of an eccentric target(Gabor,10 deg to the left of fixation)was clockwise or counter-clockwise.The target was surrounded by four distractor Gabors,thus making discrimination more difficult using peripheral vision.The target’s orientation varied 10°clockwise to 10°counter-clockwise in 1°intervals.Each participant performed four blocks of 75 trials each per day over 10 days,the first day being a baseline as the participant were tested without any scotoma.We measured discrimination performance and precision(position of the eye in X and Y).Results:Results showed similar patterns of discrimination reaction time and accuracy as well as changes to eye position for both the visible and the invisible scotoma conditions.Discrimination time significantly decreased on the last day of training compared to the first(first day M=2,965 ms,last day M=1,567 ms,P<0.05),while accuracy increased though not significantly so(first day=87.4%,last day=93.15%).There was no change in the final horizontal(X)position of first saccade relative to the target(first=−0.4°,last=−0.13°)but there was a significant upward shift(first=0.08°vs.last=0.58°,P<0.05);participants shifted their eye position on the Y axis so that they were looking at a point slightly above the target.Conclusions:These findings suggest that the presence of an artificial central scotoma induces both changes in saccade planning mechanisms as well as changes in peripheral visual function,possibly attentional,resulting in improved discrimination performance.This study allows a better comprehension of eye movement and attentional strategies during central visual loss and provides insight into possible rehabilitation strategies.

AB016.Cholinergic enhancement reduces the temporary shift in perceptual eye dominance induced by a few hours of monocular occlusion

Background:A few hours of monocular deprivation with a diffuser eye patch temporarily strengthens the contribution of the deprived eye to binocular vision.This shift in favour of the deprived eye is characterized as a form of adult visual plasticity.Studies in animal and human models suggest that neuromodulators can enhance adult brain plasticity in general.Specifically,acetylcholine has been shown to improve certain aspects of visual function and plasticity in adulthood.We investigated whether a single administration of donepezil(a cholinesterase inhibitor)could further augment the temporary shift in perceptual eye dominance that occurs after two hours of monocular patching.Methods:We conducted three experiments to investigate whether donepezil enhances the shift in perceptual eye dominance induced by monocular patching.In each experiment,healthy adults completed two experimental sessions while taking either donepezil(5 mg,oral)or a placebo(lactose)pill.In experiment 1 we patched the non-dominant eye for 2 hours and measured ocular balance with a binocular phase combination task.In experiment 2 we patched for one hour to investigate whether donepezil shortens the amount of time necessary to observe a shift in ocular dominance.In experiment 3 we patched for 2 hours and measured ocular balance with a binocular rivalry task to see if the effect of donepezil was comparable across the two tasks.We calculated AUCs for the shift in perceptual eye dominance across five time points after removing the patch to compare our treatment conditions in each experiment.Results:Donepezil significantly reduces the magnitude and duration of the shift in perceptual eye dominance produced by both 2(P<0.01)and 1 hours(P<0.05)of monocular patching when measuring ocular balance with a binocular phase combination task.Donepezil also reduces the magnitude of the shift in ocular dominance when measuring balance with a binocular rivalry task.Conclusions:Previous studies have demonstrated that cholinergic potentiation enhances adult brain plasticity.Because of this,we hypothesized donepezil would further augment the strength of the deprived eye after patching.Our study demonstrates that enhanced cholinergic potentiation actually interferes with the consolidation of the perceptual eye dominance plasticity induced by several hours of monocular deprivation.These results contribute to the growing evidence that cholinergic potentiation enhances certain forms of adult brain plasticity at the expense of others.

AB053.Oscillatory activity specific to peripheral emotional treatment induced by a visual steady state

Background:Research suggests that the analysis of facial expressions by a healthy brain would take place approximately 170 ms after the presentation of a facial expression in the superior temporal sulcus and the fusiform gyrus,mostly in the right hemisphere.Some researchers argue that a fast pathway through the amygdala would allow automatic and early emotional treatment around 90 ms after stimulation.This treatment would be done subconsciously,even before this stimulus is perceived and could be approximated by presenting the stimuli quickly on the periphery of the fovea.The present study aimed to identify the neural correlates of a peripheral and simultaneous presentation of emotional expressions through a frequency tagging paradigm.Methods:The presentation of emotional facial expressions at a specific frequency induces in the visual cortex a stable and precise response to the presentation frequency[i.e.,a steady-state visual evoked potential(ssVEP)]that can be used as a frequency tag(i.e.,a frequency-tag to follow the cortical treatment of this stimulus.Here,the use of different specific stimulation frequencies allowed us to label the different facial expressions presented simultaneously and to obtain a reliable cortical response being associated with(I)each of the emotions and(II)the different times of presentations repeated(1/0.170 ms=~5.8 Hz,1/0.090 ms=~10.8 Hz).To identify the regions involved in emotional discrimination,we subtracted the brain activity induced by the rapid presentation of six emotional expressions of the activity induced by the presentation of the same emotion(reduced by neural adaptation).The results were compared to the hemisphere in which attention was sought,emotion and frequency of stimulation.Results:The signal-to-noise ratio of the cerebral oscillations referring to the treatment of the expression of fear was stronger in the regions specific to the emotional treatment when they were presented in the subjects peripheral vision,unbeknownst to them.In addition,the peripheral emotional treatment of fear at 10.8 Hz was associated with greater activation within the Gamma 1 and 2 frequency bands in the expected regions(frontotemporal and T6),as well as desynchronization in the Alpha frequency bands for the temporal regions.This modulation of the spectral power is independent of the attentional request.Conclusions:These results suggest that the emotional stimulation of fear presented in the peripheral vision and outside the attentional framework elicit an increase in brain activity,especially in the temporal lobe.The localization of this activity as well as the optimal stimulation frequency found for this facial expression suggests that it is treated by the fast pathway of the magnocellular layers.

AB003.Pulvinar mediates the transmission of gamma and alpha oscillatory bandsbetween areas 17 and 21a

Background:Cortical activity across the visual hierarchy has different oscillatory ranges.While 25-90 Hz gamma band influences the feedforward processing,6-13 Hz alpha band travels in the feedback direction.Furthermore,gamma band acts in supragranular layers,whereas alpha range is localized in infragranular cortical layers.Is the pulvinar,the largest visual thalamic nucleus,mediating this oscillatory cortical coupling?We investigated this question by inactivating pharmacologically the pulvinar in cats and analyzing its impact on the oscillatory flow of neural activity in the visual cortex.Methods:Extracellular responses to full-field 100%contrast gratings were recorded in cortical areas 17 and 21a,from anesthetized cats using linear silicon probes before,during and after the pulvinar inactivation(injection of GABA solution).Visual stimuli were presented in one selected direction.Local field potentials(LFPs)were obtained from low-pass filtering of raw recordings.Wavelet and Granger causality analyses were performed on LFPs to determine the oscillatory coupling between cortical layers.Results:We found that cortical oscillatory activity was enhanced during LPl inactivation.These increases were observed for alpha and gamma bands in areas 17 and 21a.In area 17,alpha and gamma bands significantly increased in layers IV,V,and IV.In area 21a,this increase was observed in all layers except layer I,with a substantial increase of gamma activity in layer IV.Granger causality analysis showed that the pulvinar inactivation caused enhanced of feedforward gamma band signals from area 17(layer III)to area 21a(layer IV).For the feedback coupling,the alpha band rose from area 21a(layer V)to area 17(layers III,V,and VI).Conclusions:Our findings suggest that the pulvinar mediates the cortical oscillatory transmission between areas 17 and 21a.In particular,during the visual stimulation,the pulvinar mediates,to some extent,the bottom-up regulation from layer III of area 17 to layer IV in area 21a.Furthermore,the LPl regulates the feedback directionality of the alpha band from layer V in area 21a to layers II,V,and VI in area 17.These results contribute to our understanding of the mechanism underlying the oscillatory coupling of the feedforward and feedback processing throughout the visual cortical hierarchy.

AB055.Eye movements in the dark:saccades to non-visual targets

Background:Saccades are rapid and abrupt eye movements that allow us to change the point of fixation very quickly.Saccades are generally made to visual points of interest,but we can also saccade to non-visual objects that attract our attention.While there is a plethora of studies investigating saccadic eye movements to visual targets,there is very little evidence of how eye movement planning occurs when individuals are performing eye movements to non-visual targets across different sensory modalities.Methods:Fifteen adults with normal,or corrected to normal,vision made saccades to either visual,auditory,tactile or proprioceptive targets.In the auditory condition a speaker was positioned at one of eight locations along a circle surrounding a central fixation point.In the proprioceptive condition the participant’s finger was placed at one of the eight locations.In the tactile condition participants were touched on their right forearm in one of four eccentric location,left and right of a central point.Eye movements were made in complete darkness.Results:We compared the precision and accuracy of the eye movements to tactile,proprioceptive,and auditory targets in the dark.Overall,both precision and accuracy of movements to non-visual targets were significantly lower compared to visual targets.Conclusions:These differences emphasize the central role of the visual system in saccade planning.

AB040.Single-cell transcriptomics identifies cell-specific signatures of pathological angiogenesis

Background:To treat vascular proliferative diseases,anti-VEGF therapies have shown systemic adverse effects attributable to the lack of selectivity between pathological and physiological angiogenesis.Thus,identifying the molecular mechanisms that are only specific to pathological cell types is crucial to develop better precision medicine.Methods:Here,we used different cell type enrichment approaches combined with single-cell RNA sequencing to define the transcriptomic changes within each retinal cell types in a mouse model of ischemic retinopathy.This retinal model develops pathological neovascularization(NV)in response to local hypoxia following oxygen-induced vessel obliteration(P7 to P12).The NV phenotype is characterized by the progressive appearance of vascular tufts resulting from misguided,abnormal proliferation of endothelial cells that we monitored at 3 consecutive time points-P12,P14 and P17(peak of NV).Results:By following the dynamic response to hypoxia,our experimental design reveals how pathological angiogenesis is specifically associated with significant metabolic adaptations in different subtypes of endothelial cells(i.e.,Tips vs Stalk cells).We also identify a pathological subtype of glial cells over-expressing VEGFA and pro-inflammatory IL-1 receptor subunits.This subtype of activated glial cells was targeted using selective IL1R antagonist treatment which reduced glial activation,inflammation,NV and promotes physiological angiogenesis,therefore improving tissue regeneration.Conclusions:Our results illustrate how analyzing cell type heterogeneity in tissues developing pathological angiogenesis allows establishing better targeting therapies to restore vascular integrity.

AB092.Database for the anatomopathological,functional and surgical characterization of the cornea

Background:The purpose of this infrastructure is to provide to the Network researchers a database and diverse related tools for the anatomical and functional analysis of the normal,pathological and surgical cornea.Methods:This database is composed of normal and pathological individuals,totaling more than 36,000 patients.It includes anatomical and functional imaging data,physiological optics data,psychometric and clinical data(medical history,surgical parameters,acuteness,etc.).Various corneal topography tools were added,giving the database a unique character:tools for analyzing individual maps,average map tools for the study and comparison of populations,3D modeling and visualization tools,statistical tools,etc.There are also screening tools for detecting various corneal conditions(LASIK,PRK,RK,keratoconus)and for secure data exchange between colleagues.Results:Several studies were made in recent years thanks to this common infrastructure.For example,this database has provided important information regarding the evolution of the 3D shape of the normal cornea with age and ametropia and has confirmed the mirror symmetry of corneas for the right and the left eyes(enantiomorphism).The different stages of Fuchs’dystrophy were also characterized to provide essential knowledge for surgery of the posterior layer of the cornea.Our database also allowed studying the anatomy of the wounds and the shape of the cornea before and after a transfixing transplant or an endothelial transplant(DSAEK and DSEK).The data on the characterization of experimentally transplanted corneas with corneal equivalents generated by tissue engineering and the recent addition of clinical data on the replacement of a diseased cornea with a synthetic corneal equivalent(keratoprosthesis)also resulted in several publications.More recently,the database has allowed to develop innovative algorithms to determine the optimal shape of an implant according to the clinical parameters of the recipient.On the other hand,we also demonstrated that the 3D shape of the cornea can be used as a biometric characteristic(such as fingerprints)for identification of individuals for various applications ranging from forensics to secure border crossings.Consequently,a new multimodal database(cornea+iris+eventually retina)was created for the purpose of biometric identifications.This database provides a unique set of anatomical and functional tools for the analysis of the cornea.It is characterized by the scientific quality and large quantity of accumulated information on the cornea and the high-level tools to exploit its content.Conclusions:The common infrastructure is easily accessible to all VHRN members on request.The database will also be accessible online in 2018(see http://cvl.concordia.ca for more information).

AB041.The implication of miRNA let-7f in retinal pigment epithelium degeneration under oxidative stress

Background:Age-related macular degeneration(AMD)is the most suspected cause of vision loss in the elderly.Given the considerable evidence,oxidative stress is thought to be a primary contributing factor to AMD.Retinal pigment epithelium(RPE)could be detrimentally compromised by oxidative stress along which blebs called retinal microparticles(RMPs)start to shed.In continue these particles would be taken by retina,causing RPE senescence,dysfunction and ultimately cell death.Along with the intracellular damages,accumulative deposit of microparticles in subretinal region can cause most known histological hallmark of dry AMD namely drusen.Based on our preliminary study,of 20 present miRNAs,Let-7f is the most abundant microRNAs in RMPs.As the accused substrate of RMPs through which retina function is compromised has yet to be well understood,we aimed to investigate pathophysiological role of let-7f and specific signaling triggered in RPE dysfunction.In brief,the principal objective is to further understand how RMPs implicate in RPE dysfunction.Methods:By oxidative stress inducing,RMPs were isolated from cultured ARPE-19 cells.We considered the effect of RMPs on ARPE-19 cells viability using MTT assay.In addition,to see whether RMPs effect could be ascribed to let-7f,ARPE-19 cells were transfected by carrier containing miRNA Let-7f.These transfected cells were then subjected senescence(β-galactosidase)and cell cycle assay to explore the molecular events responsible for Let-7f induced RPE cell dysfunction.Results:Regarding result we found that RMPs adversely affected RPE cell growth and resulted in significant decrease(≥30%)in cell viability.Let-7f-treated cells also revealed considerable increases of the senescence-associatedβ-galactosidase activity.Alongside RMPs impact,let-7f treatment group also showed similar result in cell growth.Conclusions:To the best of our knowledge,RPE cells uptake microparticles derived from oxidative-injured retinal cells,deteriorating integrity of vision compartments.Not only these finding would suggest that RMP’s impression likely corresponds to the miRNA let-7f,but introduce Let-7f as a mediator exacerbating the oxidative damages to RPE cells.This undesirable interplay is followed probably by dry AMD.Taken together,it seems by finding involved downstream pathways under RMPs pathogenesis,we can inhibit AMD disease in the early stage as well.In this line,we plan to investigate consecutive effect of RMP-associated miRNA inhibition in oxidative damage of retinal pigment epithelium.

AB017.Investigation of the effect of lymphocyte-derived microparticles on retinal macrophages in the oxygen-induced retinopathy model

Background:Retinopathy of prematurity(ROP)is the major cause of blindness in children,mainly caused by the retinal neovascularization(NV).Mounting of evidences shown that macrophage plays a pivotal role in the regulation of angiogenesis in ROP.Numerous studies confirmed that the deletion of macrophage significantly reduce the neovascularized areas in the oxygen-induced retinopathy(OIR)model.We have been studied the effect of lymphocyte derived-microparticles(LMPs)over ten years.LMPs are extracellular vesicles derived from apoptotic human CEM T lymphocytes.Our previous studies demonstrated that LMPs possess strong anti-angiogenic effect.Recently we observed that LMPs are capable to switch the phenotype of macrophage,thus to suppress the choroidal neovascularization(CNV).However,the role of LMPs on macrophage in ROP has not been clarified.Thus,my project is to disclose the relationship between LMPs and macrophage in ROP using the OIR model.Hypothesis:LMPs may inhibit retinal NV in the OIR model through targeting at macrophage by affecting the migration of macrophage,thus to inhibit pathological angiogenesis in ROP.Methods:Cell culture[RAW 264.7 and bone marrow-derived macrophage(BMDM)]for cell migration and viability assay.Generate the OIR model for in vivo detection of macrophage recruitment.Quantification of retinal NV,immunohistostaining of the macrophage in vivo,ex vivo retinal explants for cell migration and qPCR.Results:LMPs do not affect RAW 264.7 and BMDM cell viability(P>0.05).LMPs significantly decrease the BMDM cell migration indirectly(P<0.05).I successfully generate the OIR model and confirm that more macrophages infiltrate during retinal angiogenesis with counting the F4/80 immunostaining in the retinal flat mount.LMPs exert inhibiting effect on retinal angiogenesis through decreasing the migration of macrophages in vivo.Conclusions:LMPs have the negative effect on retinal angiogenesis via reducing the infiltrated macrophages to the neovascularized areas in the OIR model.

AB043.Long-standing choroidal thinning in oxygen-induced retinopathy

Background:Retinopathy of prematurity(ROP),the most common cause of blindness in premature infants,has long been associated with pathologic retinal vasculature.However,recent studies reveal choroidal involution in adolescent patients formerly afflicted with ROP.We have recently demonstrated that choroidal thinning occurs early in retinopathy and persists into adulthood.Unlike retinal vessels,the damaged choroidal vasculature in ROP is incapably to regenerate.Herein,we investigated the molecular mechanism implicated in the lack of choroidal repair in ischemic retinopathy.Methods:The oxygen-induced retinopathy(OIR)model was used.Newborn Sprague-Dawley(albino)or Long-Evans rats(pigmented)rats were placed under oxygen concentration which cycles at 50%±1%or 10%±1%every 24 hours(hr)from postnatal day(P)0 to P14.On P14,all rats were returned to room air.Western blotting and qPCR were used to quantify protein and RNA abundances,respectively.The Dual-Luciferase®Reporter Assay System was used to confirm microRNA(miRNA)-mRNA interaction.Results:We detected a substantial oxidative stress in retinal pigment epithelium(RPE)and choroidal tissue,accompanied by a drastic reduction in insulin-like growth factor 1 receptor(IGF1R),a critical player in post-injury revascularization.The mechanism of decreasing IGF1R involves the over-activation of the p53 tumor suppressor that regulates miRNA let-7b,which subsequently silences Igf1r mRNA in the RPE/choroid complex of OIR subjects.Luciferase reporter assay confirmed that let-7b directly targets Igf1r mRNA at its 3’untranslated region(UTR).Indeed,silencing p53 resulted in a decreased let-7b expression,and re-established IGF1R abundance that promoted choroidal regeneration.Conclusions:Together,this study sets forth new mechanistic notion by uncovering the novel p53/let-7b/IGF1R axis;timely intervention of this pathway facilitates healthy choroidal revascularization.Future investigations on anti-angiogenic miRNAs can better our understanding on degenerative choroidopathy,such as geographic atrophy.

AB028.Mesenchymal stem cells repair retinal vascular damage in retinopathy of prematurity mouse model

Background:Retinopathy of prematurity is a leading cause of visual impairment and blindness in infants.Exposure of premature babies to the hyperoxic extrauterine environment leads to vaso-obliteration(VO),followed by ischemia,and subsequently pathological intravitreal neovascularization(NV)in the immature retina.Current treatments target only aberrant intravitreal vessel growth without repopulating the avascular regions of the retina.Thus,there is a dire need of new therapies that arrest pathological NV and promote normal retinal revascularization.Mesenchymal stem cells(MSCs)have shown the ability to migrate to the damaged tissue in different animal models and enhance vascularization.We,therefore,investigated whether MSCs can promote vascular repair in a mouse model of ROP.Methods:Oxygen-induced retinopathy(OIR)model was used herein.Postnatal day 7(P7)mice were subjected to 75%O2 until P12 to induce VO followed by 5 days of room air leading to NV.Compact bone-derived MSCs were isolated from adult C57BL/6 mice and cultured either in hypoxia(5%O2)or normoxia(21%O2).Conditioned media(CM)was collected 24 hours later and injected intravitreally in P12 OIR retinas to assess vascular repair.To determine possible factors involved in MSC-induced revascularization,gene expression analysis was performed on P17 OIR retinas.In vitro,we investigated the effect of MSC-CM on microglial polarization using quantitative PCR and flow cytometry.Results:Hypoxic MSC-CM significantly(P<0.01)decreased both VO and NV areas in comparison to the normoxic counterpart.Levels of IGF-1 and VEGF were significantly high in MSC-injected OIR retinas.Moreover,gene expression levels of pro-inflammatory cytokines(IL-1β,TNFα)dropped whereas levels of anti-inflammatory cytokines(IL-10,IL-4)increased.Treatment of pro-inflammatory M1 microglia with MSC-CM decreased the gene expression of IL-1βand TNFα,and iNOS(M1 marker)at the transcript and protein levels.Conclusions:In this study,we demonstrated that MSCs promote healthy vessel growth in OIR retinas via a paracrine fashion by regulating expression of angiogenic factors and modulating inflammation.