Aberrant GPA expression and regulatory function of red blood cells in sickle cell disease.

ABSTRACT: Glycophorin A (GPA), a red blood cell (RBC) surface glycoprotein, can maintain peripheral blood leukocyte quiescence through interaction with a sialic acid-binding Ig-like lectin (Siglec-9). Under inflammatory conditions such as sickle cell disease (SCD), the GPA of RBCs undergo structural changes that affect this interaction. Peripheral blood samples from patients with SCD before and after RBC transfusions were probed for neutrophil and monocyte activation markers and analyzed by fluorescence-activated cell sorting (FACS). RBCs were purified and tested by FACS for Siglec-9 binding and GPA expression, and incubated with cultured endothelial cells to evaluate their effect on barrier function. Activated leukocytes from healthy subjects (HS) were coincubated with healthy RBCs (RBCH), GPA-altered RBCs, or GPA-overexpressing (OE) cells and analyzed using FACS. Monocyte CD63 and neutrophil CD66b from patients with SCD at baseline were increased 47% and 27%, respectively, as compared with HS (P = .0017, P = .0162). After transfusion, these markers were suppressed by 22% and 17% (P = .0084, P = .0633). GPA expression in RBCSCD was 38% higher (P = .0291) with decreased Siglec-9 binding compared with RBCH (0.0266). Monocyte CD63 and neutrophil CD66b were suppressed after incubation with RBCH and GPA-OE cells, but not with GPA-altered RBCs. Endothelial barrier dysfunction after lipopolysaccharide challenge was restored fully with exposure to RBCH, but not with RBCSCD, from patients in pain crisis, or with RBCH with altered GPA. Pretransfusion RBCSCD do not effectively maintain the quiescence of leukocytes and endothelium, but quiescence is restored through RBC transfusion, likely by reestablished GPA-Siglec-9 interactions.

Amphipathic Helical Peptide L37pA Protects against Lung Vascular Endothelial Dysfunction Caused by Truncated Oxidized Phospholipids via Antagonism with CD36 Receptor.

The generation of bioactive truncated oxidized phospholipids (Tr-OxPLs) from oxidation of cell-membrane or circulating lipoproteins is a common feature of various pathological states. Scavenger receptor CD36 is involved in lipid transport and acts as a receptor for Tr-OxPLs. Interestingly, Tr-OxPLs and CD36 are involved in endothelial dysfunction-derived acute lung injury, but the precise mechanistic connections remain unexplored. In the present study, we investigated the role of CD36 in mediating pulmonary endothelial cell (EC) dysfunction caused by Tr-OxPLs. Our results demonstrated that the Tr-OxPLs KOdia-PC, Paz-PC, PGPC, PON-PC, POV-PC, and lysophosphocholine caused an acute EC barrier disruption as revealed by measurements of transendothelial electrical resistance and VE-cadherin immunostaining. More importantly, a synthetic amphipathic helical peptide, L37pA, targeting human CD36 strongly attenuated Tr-OxPL-induced EC permeability. L37pA also suppressed Tr-OxPL-induced endothelial inflammatory activation monitored by mRNA expression of inflammatory cytokines/chemokines and adhesion molecules. In addition, L37pA blocked Tr-OxPL-induced NF-κB activation and tyrosine phosphorylation of Src kinase and VE-cadherin. The Src inhibitor SU6656 attenuated KOdia-PC-induced EC permeability and inflammation, but inhibition of the Toll-like receptors (TLRs) TLR1, TLR2, TLR4, and TLR6 had no such protective effects. CD36-knockout mice were more resistant to Tr-OxPL-induced lung injury. Treatment with L37pA was equally effective in ameliorating Tr-OxPL-induced vascular leak and lung inflammation as determined by an Evans blue extravasation assay and total cell and protein content in BAL fluid. Altogether, these results demonstrate an essential role of CD36 in mediating Tr-OxPL-induced EC dysfunction and suggest a strong therapeutic potential of CD36 inhibitory peptides in mitigating lung injury and inflammation.

Seasonal Hyperacute Panuveitis (SHAPU) Outbreak Amidst COVID-19 Pandemic.

PURPOSE: To document the demographic profile of the SHAPU outbreak amidst the COVID-19 pandemic. METHODS: A multicentric cross-sectional study of the 2021 SHAPU outbreak during the second phase of the COVID-19 outbreak. RESULTS: A total of 135 patients were diagnosed with SHAPU from August to December 2021, 77 (57%) were children <16 years, males 54.8% and 34.8% had direct physical contact with white moths and 41.5% had severe type of SHAPU. Dramatic increment in the moth abundance was noted in these outbreak sites. Few cases presented with atypical ocular findings, unlike past outbreaks. Due to the ongoing COVID-19 pandemic with restrictions on travel and transportation, timely management was difficult and good visual outcome was achieved only in mild-moderate cases with an early presentation. CONCLUSION: The surge in the number of SHAPU patients, its occurrence in areas previously unreported, and some atypical presentation added raised suspicion of a possible link between COVID-19 and SHAPU.

Increase in SHAPU patients, incidence in unreported areas of Nepal, atypical ocular presentations and shift in disease affection from children towards adults population have raised doubt between connections between SHAPU, white moths and COVID pandemic.

Purtscher-like retinopathy with serous macular detachment in a case of acute pancreatitis: A case report.

A 28-year-old male hospitalized with a diagnosis of acute pancreatitis presented with sudden onset of blurred vision in both eyes after 48 h of admission. Visual acuity was counting fingers in both eyes. Fundus examination revealed multiple cotton wool spots and intraretinal hemorrhages typical of Purtscher's retinopathy. Optical coherence tomography macula showed serous macular detachment. In 8 weeks follow-up, visual acuity improved to 6/18 oculus dexter (OD) and 6/60 oculus sinister (OS) with resolution of fundus lesions and resorbed subretinal fluid. Purtscher-like retinopathy, though rare should be considered as a differential in all cases with vision loss in acute pancreatitis. This particular case highlights the significance of a thorough examination of the fundus by an ophthalmologist in identifying this infrequent condition that is often overlooked.

Endogenous endophthalmitis in post-COVID-19 patients: a case report.

Ocular involvement in coronavirus disease 2019 (COVID-19) can be due to direct viral invasion or indirectly due to an immunosuppressed state. Prolonged hospitalization also makes them susceptible to various secondary infections. The purpose of this case report is to report two rare cases of endogenous endophthalmitis (EE) in COVID-19 recovered patients. Case presentation: Two patients who were hospitalized and received treatment for COVID-19 pneumonia with remdesivir and systemic steroids presented with decreased vision. The first case had a severe anterior chamber reaction with a hypopyon and dense exudates in the vitreous. The second case had cells and flare in the anterior chamber and exudates in the vitreous. They were diagnosed with EE and underwent a diagnostic vitreous tap followed by pars plana vitrectomy and intravitreal antibiotic and steroid. The culture of vitreous fluid was negative for any bacteria and fungus in both cases. However, the first case demonstrated Escherichia coli in urine culture. The follow-up visual acuity was no perception of light and only perception of light in the first and second case, respectively. Clinical discussion: Severe COVID-19 patients who are hospitalized, receive systemic steroid and have associated comorbidities like diabetes mellitus are at high risk of EE. Conclusion: Delay in diagnosis and appropriate treatment in these patients leads to poor visual outcome.

Aging-Related Accumulation of Truncated Oxidized Phospholipids Augments Infectious Lung Injury and Endothelial Dysfunction via Cluster of Differentiation 36-Dependent Mechanism.

Truncated phospholipid oxidation products (Tr-OxPL) increase in blood circulation with aging; however, their role in the severity of vascular dysfunction and bacterial lung injury in aging groups remains poorly understood. We investigated the effects of six Tr-OxPL species: KOdiA-PC, POVPC, PONPC, PGPC, Paz-PC, and Lyso-PC on endothelial dysfunction and lung inflammation caused by heat-killed Staphylococcus aureus (HKSA) in young (aged 2-4 months) and old (aged 12-18 months) mice, organotypic culture of precisely cut lung slices, and endothelial cells (mLEC) isolated from young and old mice. HKSA and Tr-OxPL combination caused a higher degree of vascular leak, the accumulation of inflammatory cells and protein in bronchoalveolar lavage, and inflammatory gene expression in old mice lungs. HKSA caused a greater magnitude of inflammatory gene activation in cell and ex vivo cultures from old mice, which was further augmented by Tr-OxPLs. L37pA peptide targeting CD36 receptor attenuated Tr-OxPL-induced endothelial cell permeability in young and old mLEC and ameliorated KOdiA-PC-induced vascular leak and lung inflammation in vivo. Finally, CD36 knockout mice showed better resistance to KOdiA-PC-induced lung injury in both age groups. These results demonstrate the aging-dependent vulnerability of pulmonary vasculature to elevated Tr-OxPL, which exacerbates bacterial lung injury. CD36 inhibition is a promising therapeutic approach for improving pneumonia outcomes in aging population.

Truncated oxidized phospholipids exacerbate endothelial dysfunction and lung injury caused by bacterial pathogens.

Oxidized phospholipids (OxPLs) are present at basal levels in circulation of healthy individuals, but a substantial increase and changes in composition of OxPLs may rapidly occur during microbial infections, sepsis, and trauma. Specifically, truncated oxidized phospholipids (Tr-OxPLs) exhibit detrimental effects on pulmonary endothelium, yet their role on modulation of lung injury caused by bacterial pathogens remains to be elucidated. This study investigated the effects of Tr-OxPL species: KOdiA-PC, POV-PC, PON-PC, PAz-PC, PGPC, and Lyso-PC on endothelial permeability and inflammatory responses to gram-positive bacterial particles. Results showed that all six tested Tr-OxPLs augmented endothelial barrier disruption caused by heat-killed Staphylococcus aureus (HKSA) as determined by VE-cadherin immunostaining and monitoring transendothelial electrical resistance. In parallel, even moderate elevation of Tr-OxPLs augmented HKSA-induced activation of NF-κB, secretion of IL-6 and IL-8, and protein expression of ICAM-1 and VCAM-1. In the mouse model of acute lung injury caused by intranasal injection of HKSA, intravenous Tr-OxPLs administration augmented HKSA-induced increase in BAL protein content and cell counts, tissue expression of TNFα, KC, IL1ß, and CCL2, and promoted vascular leak monitored by lung infiltration of Evans Blue. These results suggest that elevated Tr-OxPLs act as critical risk factor worsening bacterial pathogen-induced endothelial dysfunction and lung injury.

Role of multimodal imaging in differentiating unilateral APMPPE from unilateral Harada disease - a case report.

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is classified as a part of the spectrum of the white dot syndromes affecting the inner choroid and the outer retina. It is usually bilateral and affects young patients between the second and fourth decades. The authors report an unusual case of unilateral APMPPE mimicking Vogt-Koyanagi-Harada (VKH) disease where the fundus fluorescein angiography was instrumental in confirming the diagnosis. Case presentation: A 35-year-old male presented with decreased visual acuity in the right eye for 3 days. Fundus examination revealed minimal vitritis, disc edema, and multifocal yellowish placoid lesions. Optical coherence tomography (OCT) showed the accumulation of subretinal fluid with subretinal septations closely mimicking VKH. Fundus fluorescein angiography depicted features of early hypofluorescence and late staining of the placoid lesions, suggesting APMPPE. Subretinal fluid partly resolved within a week, and visual acuity improved to 6/9(20/30) in the affected eye after the use of oral NSAIDS. Complete resolution of subretinal fluid was seen after 6 weeks. Clinical discussion: The most distinguishing feature in this case is the unilateral presentation and macular serous retinal detachment with subretinal septa on OCT imaging, which are not the typical features in APMPPE but quite similar to the characteristic features in acute VKH disease. Conclusion: APMPPE and acute VKH disease may share some overlapping clinical manifestations and imaging findings on OCT. APMPPE is a self-resolving disease, unlike VKH, and early diagnosis can avoid unnecessary administration of steroids and related side effects.

Mechanisms of pulmonary endothelial permeability and inflammation caused by extracellular histone subunits H3 and H4.

Extracellular DNA-binding proteins such as histones are danger-associated molecular pattern released by the injured tissues in trauma and sepsis settings, which trigger host immune response and vascular dysfunction. Molecular events leading to histone-induced endothelial cell (EC) dysfunction remain poorly understood. This study performed comparative analysis of H1, H2A, H2B, H3, and H4 histone subunits effects on human pulmonary EC permeability and inflammatory response. Analysis of transendothelial electrical resistance and EC monolayer permeability for macromolecues revealed that H3 and H4, but not H1, H2A, or H2B caused dose-dependent EC permeability accompanied by disassembly of adherens junctions. At higher doses, H3 and H4 activated nuclear factor kappa B inflammatory cascade leading to upregulation EC adhesion molecules ICAM1, VCAM1, E-selectin, and release of inflammatory cytokines. Inhibitory receptor analysis showed that toll-like receptor (TLR) 4 but not TLR1/2 or receptor for advanced glycation end inhibition significantly attenuated deleterious effects of H3 and H4 histones. Inhibitor of Rho-kinase was without effect, while inhibition of Src kinase caused partial preservation of cell-cell junctions, H3/H4-induced permeability and inflammation. Deleterious effects of H3/H4 were blocked by heparin. Activation of Epac-Rap1 signaling restored EC barrier properties after histone challenge. Intravenous injection of histones in mice caused elevation of inflammatory markers and increased vascular leak. Post-treatment with pharmacological Epac/Rap1 activator suppressed injurious effects of histones in vitro and in vivo. These results identify H3 and H4 as key histone subunits exhibiting deleterious effects on pulmonary vascular endothelium via TLR4-dependent mechanism. In conclusion, elevation of circulating histones may represent a serious risk of exacerbated acute lung injury (ALI) and multiple organ injury during severe trauma and infection.

Causes and Managements of Early-Onset Ocular Hypertension Following Pars Plana Vitrectomy with Silicone Oil for Retinal Detachment and Exploration of Trabeculectomy as a Viable Alternative Management: A Pilot Study.

INTRODUCTION: This study aims to study a relatively unexplored topic about the causes and managements of early-onset ocular hypertension (OHTN) following the pars plana vitrectomy with silicone oil (PPV with SO) procedure for retinal detachment. Additionally, to explore the outcome of trabeculectomy in managing such patients. MATERIALS AND METHODS: This is a retrospective exploratory pilot study. We studied 23 patients who underwent the procedure then subsequently developed ocular hypertension within a month of the procedure. The probable causes for their early-onset ocular hypertension were identified and addressed with medicine, peripheral iridotomy (PI), complete or partial silicone removal. Trabeculoplasty was done in irretractable causes. This study aimed to evaluate the causes of early onset ocular hypertension after pars plana vitrectomy with silicone oil and explore the outcome of different managements including trabeculectomy. RESULTS: Inflammation (n=11, 47.8%) was the most common cause of early-onset ocular hypertension. Other causes were overfilling/spilling of silicone oil in anterior chamber (n=5, 21.7%), pupillary block (n=4, 17.4%) and angle-recession glaucoma (n=2, 8.69%). Majority of the cases responded to intraocular pressure (IOP) lowering medications (n=11). Three eyes with persistently high intraocular pressure underwent trabeculectomy after which the intraocular pressure was controlled. CONCLUSION: Even though prior studies have reported that trabeculectomy does not address late-onset ocular hypertension, our study shows that the procedure might be helpful in early-onset ocular hypertension. This is probably because at the time of presentation for early-onset ocular hypertension, silicone has not emulsified, which will not be the case in late-onset ocular hypertension. If a large study also shows that trabeculectomy can correct early-onset ocular hypertension, this information can guide the practices of ophthalmologists whose patients cannot afford expensive glaucoma drainage devices.

Circulating extracellular histones exacerbate acute lung injury by augmenting pulmonary endothelial dysfunction via TLR4-dependent mechanism.

Extracellular histones released into the circulation following trauma, sepsis, and ARDS may act as potent damage-associated molecular pattern signals leading to multiple organ failure. Endothelial cell (EC) dysfunction caused by extracellular histones has been demonstrated in vitro and in vivo; however, precise mechanistic details of histone-induced EC dysfunction and exacerbation of ongoing inflammation remain poorly understood. This study investigated the role of extracellular histones in exacerbating preexisting endothelial dysfunction and acute lung injury. Histone subunits H3 and H4, but not H1, H2A, or H2B, induced permeability in human pulmonary EC. H3 and H4 at concentrations above 30 µg/mL caused EC inflammation reflected by activation of the NF-κB pathway, transcriptional activation, and release of cytokines and chemokines including IL-6 and IL-8, and increased mRNA and protein expression of EC adhesion molecules VCAM-1 and ICAM-1. Pharmacological inhibitors targeting Toll-like receptor TLR4 but not TLR2/6, blocked histone-induced EC dysfunction. H3 and H4 also strongly augmented EC permeability and inflammation caused by Gram-negative and Gram-positive bacterial particles, endotoxin, and TNFα. Heparin blocked histone-induced augmentation of EC inflammation caused by endotoxin and TNFα. Injection of histone in mouse models of lung injury caused by bacterial wall lipopolysaccharide (LPS) and heat-killed Staphylococcus aureus (HKSA) augmented ALI parameters: increased protein content, cell count, and inflammatory cytokine secretion in bronchoalveolar lavage fluid. Important clinical significance of these findings is in the demonstration that even a modest increase in extracellular histone levels can act as a severe exacerbating factor in conjunction with other EC barrier disruptive or proinflammatory agents.

Panophthalmitis secondary to retained intraocular foreign body amidst a national lockdown during the COVID-19 pandemic: A case series and review of literature.

Introduction: Intraocular foreign bodies (IOFBs) can be serious as they may result in vision-threatening ocular inflammations and even loss of the eye. Delay in presentation or treatment by more than 24 hours from the time of injury results in a poor prognosis. In penetrating wounds, microorganisms enter the eye through penetrating objects. Both bacterial and fungal organisms are responsible for causing panophthalmitis. At the ocular level, these microorganisms produce irreversible damage which includes keratitis, uveitis, hypopyon, vitreous abscesses, retinal necrosis, detachment, and, finally, panophthalmitis. Case scenarios: In this case series, we report three cases of IOFB presenting with panophthalmitis secondary to delay in seeking medical attention. In our cases, there was a delay in the presentation by more than 24 hours of trauma. All cases had panophthalmitis at the time of presentation. In two cases, the causative organism was coagulase-negative staphylococci and in one case it was staphylococcus. Initially, we planned to manage them with intravitreous, intravenous and topical antibiotics till the inflammation subsides, then IOFB removal surgeries were planned. However, in two cases, the clinical presentation worsens with scleral necrosis. Therefore, they had to undergo evisceration. In one case, the antibiotics therapy was enough without IOFB removal surgery to manage her symptoms. All cases recovered uneventfully after the interventions. Discussion/Conclusion: In developing nations, like Nepal, transportation barriers can affect a person's access to health care services. This can be clearly explained from this case series as limited transportation options in rural regions are a major factor for all patients' delayed presentation to the hospital during the time of national lockdown in the second wave of the COVID-19 pandemic. The concerned authority must pay attention to solving such social determinants of health.

Optical coherence tomography patterns of diabetic macular edema and treatment response to bevacizumab: a short-term study.

Background: The purpose of this study was to evaluate the short-term response of intravitreal bevacizumab in diabetic macular edema (DME) and assess the variation in treatment outcomes in different morphology patterns using spectral domain-optical coherence tomography (SD-OCT). Objective: To study different morphological patterns of DME based on OCT and compare their treatment response to bevacizumab. Methods: Hundred and twelve eyes of 112 patients with DME were included and treated with intravitreal bevacizumab (1.25 mg/0.05 ml monthly for 3 months). The morphological patterns of DME were classified on the basis of OCT into three groups - diffuse retinal thickening (DRT), cystoid macular edema (CME), and serous retinal detachment (SRD) - and changes in central macular thickness (CMT) and best corrected visual acuity (BCVA) after treatment were compared. Results: A total of 112 eyes with DME were included and consisted of 40 DRT, 37 CME, and 35 SRD. Treatment with bevacizumab resulted in decrease in central macular thickness and improvement in BCVA in all three groups. The baseline visual acuity and CMT of DRT group was better than that of the other two groups. The treatment outcome was measured in terms of CMT and BCVA. Change in CMT was statistically significant among three groups and was found to be better in DRT group (p < 0.05, 95% confidence interval). However, there was statistically no significant variation between the three groups regarding the change in BCVA (p = 0.169, 95% confidence interval). Conclusion: Anatomic and visual improvement can be achieved by bevacizumab in all patterns of DME. However, individual pattern may respond differently. DRT, which appears to be the earliest form of DME, responds better than other types. Thus, the pattern of macular edema shown by OCT may provide an objective guideline in predicting the response of bevacizumab injection in DME.

Classification of Seasonal Hyperacute Panuveitis (SHAPU).

INTRODUCTION: Classification are essential part of scientific methodology and has important role in medical reporting system. Even after having 46 years long history, Seasonal Hyperacute Panuveitis (SHAPU), the blinding diseases reported mainly from Nepal lacks a standard classification system. Thus, we aim to contribute in the ophthalmic nosology by purposing a classification system for SHAPU. METHODOLOGY: The classification is suggested on the background of prolonged experience of this entity by the group of investigators who have dedicated years of research on this topic. CONCLUSION: We are optimistic that the proposed classification system will help in effective planning and evaluation of this ocular emergency condition and deliver the appropriate and reliable information for timely management and prevention of complications.

Influence of glycaemic control on macular thickness in diabetic retinopathy.

INTRODUCTION: Diabetic macular oedema (DME) is one of the major cause of decreased visual acuity in patients with diabetic retinopathy. Poor glycaemic control is associated with increased incidence of DME. METHODS: A total of 112 eyes of 112 patients were studied in this cross-sectional study and were classified into three groups based on HbA1c: group 1 included patients with good glycaemic control (HbA1c ≤7%), group 2 included patients with moderate glycaemic control (HbA1c between 7% and 9%) and group 3 included patients with poor glycaemic control (HbA1c ≥9%). RESULTS: We included 112 eyes of 112 patients. The mean duration of diabetes mellitus (DM) was 11.37 years. In statistical analysis, CMT (mean 188.80 ± 27.64 µm) positively correlated with mean HbA1c level (7.95 ± 1.29%) (r = 0.238, p < .05). There was a significant difference in CMT values among the three groups of HbA1c (F (2,109) = 19.39, p < .001). Post hoc analysis showed statistical significance between HbA1c≤7% and HbA1c ≥9% group and HbA1c 7%-9% and ≥9% group. However, statistical significance was not found among HbA1c ≤7% group and HbA1c 7%-9% group. Multiple regression analyses showed a significant correlation between CMT and HbA1c after adjusting for age and duration of diabetes. CONCLUSION: Serum HbA1c level has a significant correlation with CMT in diabetic patients.

Does outer retinal layer thickness correlate with the central visual field indices in early dry age-related macular degeneration?

PURPOSE: Age-related macular degeneration (ARMD) is the leading cause of irreversible blindness worldwide and Nepal is one among them. We aimed to determine the relationship between outer retinal layer thickness parameters with central visual field indices in early dry ARMD cases among Nepalese population. MATERIALS AND METHODS: The subjects for this descriptive, cross-sectional study comprised 40 patients with early dry ARMD from the ophthalmology department of a tertiary level hospital of Nepal. The retinal layer thickness was measured with spectral-domain optical coherence tomography (SD-OCT), and the visual field indices were assessed using the 10-2 protocol of Humphrey visual field analyzer (HFA). Thus, the retinal layer structures correlated with visual field indices among our population. RESULTS: Among our early dry ARMD population, the foveal threshold (FT) was found to be significantly correlated with retinal pigment epithelium (RPE) elevation (P < 0.01, r = -0.541), outer segment (OS) length (P = 0.02, r = 0.465), and inner segment ellipsoid (ISe) band disruption (P = 0.01, r = -0.499), but not with presence of hyperreflective foci (P = 0.464), RPE thickness (P = 0.612), and central macular thickness (P = 0.214). However, no significant correlation between mean deviation and pattern standard deviation of visual field with retinal layer thickness parameters was identified. CONCLUSION: In early dry ARMD, a reduced FT is significantly correlated with the integrity of the ISe band, thinning of OS length, and drusen-associated RPE elevation. The results highlight the utility of both SD-OCT retinal layer measurement and central visual field testing by HFA in ARMD to monitor the progression of the disease.

Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury.

Earlier studies investigating the pathogenesis of chronic vascular inflammation associated with atherosclerosis described pro-inflammatory and vascular barrier disruptive effects of lipid oxidation products accumulated in the sites of vascular lesion and atherosclerotic plaque. However, accumulating evidence including studies from our group suggests potent barrier protective and anti-inflammatory properties of certain oxidized phospholipids (OxPLs) in the lung vascular endothelium. Among these OxPLs, oxidized 1-palmitoyl-2-arachdonyl-sn-glycero-3-phosphocholine (OxPAPC) causes sustained enhancement of lung endothelial cell (EC) basal barrier properties and protects against vascular permeability induced by a wide variety of agonists ranging from bacterial pathogens and their cell wall components, endotoxins, thrombin, mechanical insults, and inflammatory cytokines. On the other hand, truncated OxPLs cause acute endothelial barrier disruption and potentiate inflammation. It appears that multiple signaling mechanisms triggering cytoskeletal remodeling are involved in OxPLs-mediated regulation of EC barrier. The promising vascular barrier protective and anti-inflammatory properties exhibited by OxPAPC and its particular components that have been established in the cellular and animal models of sepsis and acute lung injury has prompted consideration of OxPAPC as a prototype therapeutic molecule. In this review, we will summarize signaling and cytoskeletal mechanisms involved in OxPLs-mediated damage, rescue, and restoration of endothelial barrier in various pathophysiological settings and discuss a future potential of OxPAPC in treating lung disorders associated with endothelial barrier dysfunction.

Microtubules as Major Regulators of Endothelial Function: Implication for Lung Injury.

Endothelial dysfunction has been attributed as one of the major complications in COVID-19 patients, a global pandemic that has already caused over 4 million deaths worldwide. The dysfunction of endothelial barrier is characterized by an increase in endothelial permeability and inflammatory responses, and has even broader implications in the pathogenesis of acute respiratory syndromes such as ARDS, sepsis and chronic illnesses represented by pulmonary arterial hypertension and interstitial lung disease. The structural integrity of endothelial barrier is maintained by cytoskeleton elements, cell-substrate focal adhesion and adhesive cell junctions. Agonist-mediated changes in endothelial permeability are directly associated with reorganization of actomyosin cytoskeleton leading to cell contraction and opening of intercellular gaps or enhancement of cortical actin cytoskeleton associated with strengthening of endothelial barrier. The role of actin cytoskeleton remodeling in endothelial barrier regulation has taken the central stage, but the impact of microtubules in this process remains less explored and under-appreciated. This review will summarize the current knowledge on the crosstalk between microtubules dynamics and actin cytoskeleton remodeling, describe the signaling mechanisms mediating this crosstalk, discuss epigenetic regulation of microtubules stability and its nexus with endothelial barrier maintenance, and overview a role of microtubules in targeted delivery of signaling molecules regulating endothelial permeability and inflammation.

Challenges of Pediatric Cataract Surgery in a Case of Seasonal Hyperacute Panuveitis (SHAPU).

A four-year-old female child diagnosed as a case of severe Seasonal Hyperacute Panuveitis (SHAPU) underwent lens-sparing core vitrectomy in her left eye with intravitreal antibiotic and steroid. Patient responded well to treatment and intraocular inflammation subsided. However, three months later, she developed vision impairing dense cataract which also made posterior segment assessment difficult. Lens aspiration with primary posterior capsulotomy and anterior vitrectomy with intraocular lens (IOL) implantation was performed. However, four weeks later, the patient developed occlusio pupillae with iris bombe. She did not respond to medical management so synechiolysis with surgical iridectomy was performed after which a normal depth anterior chamber was attained. Synechia and iris bombe were also relieved, and vision was regained.

Sporadic summer outbreak of SHAPU in even years: Does the pattern match with the usual autumn outbreak?

PURPOSE: Seasonal Hyperacute Panuveitis (SHAPU), is a mysterious blinding disease seen only in Nepal with a higher prevalence among children usually seen in autumn every alternate odd year since 1975. This report highlights the sporadic summer outbreak in the even years with atypical presentation. OBSERVATIONS: Three patients were diagnosed as SHAPU in the summer (May) of 2020. All of them noted the presence of white moths (Gazalina species) in their environment with or without direct physical contact. The clinical patterns were severe in nature including corneal melting. Two out of three patients (66.6%) developed phthisis bulbi and lost their vision. CONCLUSIONS AND IMPORTANCE: White moth has been associated as a risk factor for SHAPU. Despite the known natural history of appearance after monsoon of every odd year, the few unhatched eggs of the moths may hatch under the favorable circumstances in the summer of the even years and may lead to the sporadic outbreak of SHAPU. Though less in numbers, the clinical presentation of such sporadic SHAPU cases may be atypical with less favorable outcome.