Oxidative stress is crucial for the morbidity of diabetic complications. An abnormal metabolic milieu as a result of hyperglycemia leads to the onset of several complications, including diabetic retinopathy (DR). Treating eye diseases like DR is challenging due to the eye’s anatomy, physiology, and biochemistry. A biological antioxidant capable of inhibiting oxidative/nitrosative stress-mediated diabetic progression during hyperglycemia is still needed. We investigated the role of silica-coated gold nanoparticles (AuNP@SiO 2 ) on high-glucose (HG)-induced oxidative stress, mitochondrial dysfunction, apoptosis, inflammation, and neurodegeneration in rat retinal ganglion cells (RGC-5). Using advanced techniques, we investigated the profound inhibitory effect of AuNP@SiO 2 in RGC-5 cells in the presence of a HG environment. Overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the HG environment weakened the endogenous antioxidants, including catalase, superoxide dismutase, and glutathione peroxidase and AuNP@SiO 2 treatment restored the HG effect. Furthermore, excess accumulation of ROS/RNS was allied with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential (ΔΨm) and increased mitochondrial mass in the HG environment, which Au@SiO 2 nanoparticles (NPs) attenuated in RGC-5 cells. Moreover, the imbalance between the generation of ROS/RNS and their corresponding weakened endogenous antioxidant defense system leads to biomolecule damage, downregulation of 8-oxo guanine glycosylase, and accumulation of deoxyguanosine (8-OHdG) in DNA. However, treatment of AuNP@SiO 2 attenuated the action. To broaden the knowledge, we further investigated the influence of AuNP@SiO 2 on HG-induced increased expression of inflammatory mediators and neurodegenerative markers, leading to apoptosis, which was attenuated by Au@SiO 2 NPs in RGC-5 cells. In summary, AuNP@SiO 2 represents a potentially promising agent for facilitating defense against HG-induced oxidative/nitrosative stress, antioxidant depletion, mitochondrial dysfunction, apoptosis, and inflammation, thus generating a sustained control over ROS/RNS, which consequently evoke the potential of AuNP@SiO 2 as an economic therapeutic remedy in diabetic treatments and its complications.

Idiopathic macular hole (IMH) is a condition that arises from a combination of interactions among several forces on the fovea, remarkably from vitreous traction in the anteroposterior and tangential directions. Recent studies have highlighted the significance of microincision vitrectomy surgery, and IMH surgery was performed with minimal invasiveness, and visual improvement was an expected outcome. This study aimed to observe the pre-operative optical coherence tomography (OCT) indices correlated with visual acuity in the closure of IMH after surgery. Primarily, the findings were associated with clinical characteristics, including OCT indices, change in best corrected visual acuity (BCVA), clinical factors associated with IMH closure, and prognostic factors for the visual outcomes. This retrospective study included pre- and post-operative BCVA and OCT indices of 110 eyes with IMH. Each OCT variable was subjected to stepwise regression analysis regarding therapeutic factors that predict the need for IMH closure. Our results revealed that the hole form factor (HFF, r = 0.196), macular hole index (MHI, r = 0.669), and tractional hole index (THI, r = 0.085) had a positive correlation with visual acuity. However, basal hole diameter (BHD, r = -0.696) and minimum hole diameter (MHD, r = -0.407) showed a negative correlation. Out of them, HFF, MHI, BHD, and MHD were observed to be statistically significant (p < 0.05). The mean follow-up time was 149 ± 63.22 (85-300) days. The mean baseline BCVA was 0.75 ± 0.44 logMAR (Logarithm of the Minimum Angle of Resolution) units, which was improved to 0.29 ± 0.27 logMAR units at the final follow-up. The surgical success closure rate was 100 % among subjects with IMH. In conclusion, OCT indices were significant indicators of visual success rates in IMH, and OCT measurement could be employed as a single key index in predicting the IMH closure rate. Also, our findings suggested that OCT indices could be utilized as a safe and effective predictor of visual and anatomical outcomes in the case of IMH.

Huntington’s disease (HD) is a progressive neurodegenerative complication of the brain that causes uncontrolled choreatic movements, memory loss, abnormal motor function, emotional changes, and a decline in cognition as well as an inability to perform daily routine tasks. The development of advanced techniques, including genetics, molecular biology, and genetic engineering, is beginning to discover an anomalous role of immune modulatory molecules in HD onset and pathophysiological complications. However, the role of immunoregulatory molecules, which are the key chemical messengers that mediate intracellular communication to regulate cellular and nuclear functions in HD pathogenesis, is still being unexplored. Here we present recent immunological association studies on HD and emerging mechanisms for the immunotherapies implicated in HD pathogenesis. The implications of immunotherapies are very critical under both healthy and HD disease conditions. Recently, research work has established new functional aspects of their pathways. Moreover, we propose future directions for immune-related research in HD pathogenesis and potential therapeutic approaches for immune-related therapies.

Growing evidences suggest that excess generation of highly reactive free oxygen/nitrogen radicals (ROS/RNS) are largely due to hyperglycemia causes oxidative stress. Further, excess accumulation of ROS/RNS in cellular compartments aggravates the development and progression of diabetes and its associated complications. Impaired wound healing in diabetic condition is a known vital complication all around the world. Thus, an antioxidant agent having the potential for hindering the oxidative/nitrosative stress triggered diabetic skin complication is required. The present investigation was carried out to understand the impact of silica coated gold nanoparticle (Au@SiO2 NPs) on high glucose (HG)-induced keratinocyte complications. We demonstrated that HG environment enhanced the ROS and RNS accumulations and reduced in cellular antioxidant capacities in keratinocte cells, however, Au@SiO2 NPs treatment restored the HG effect. Furthermore, excess production of ROS/RNS was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential (ΔΨm), and increased in mitochondrial mass, which was restored by Au@SiO2 NPs treatment in keratinocyte cells. In addition, HG-induced excess production of ROS/RNA caused an increased in the biomolecules damage including lipid peroxidation (LPO), and protein carbonylation (PC), 8-oxoguanine DNA glycosylase-1 (OGG1) expression and increased 8-hydroxydeoxyguanosine (8-OHdG) accumulations in DNA, leading to activation of ERK1/2MAPK, AKT and tuberin pathway, inflammatory reaction, and finally apoptotic cell death. In conclusion, our findings showed that Au@SiO2 NPs treatment improved the HG-induced keratinocytes injury by suppressing the oxidative/nitrosative stress, elevating the antioxidant defence system, thereby inhibiting the inflammatory mediators and apoptosis, which may be a therapeutic cure for the diabetic keratinocyte problems.

PDF - 161K, Effect of acacetin on TCM-stimulated capillary tube formation by HUVEC on matrigel.

Objective: To evaluate the surgical visual outcomes of three-piece rigid scleral fixated intraocular lens (SFIOL) implantation in subjects with deficient posterior capsule following complications of cataract extraction.Design: Retrospective 4-year cohort study.Participants: Data from 174 eyes that underwent SFIOL combined with pars plana vitrectomy (PPV) between January 2018 and March 2022 and follow-up exams were included.Methods: Demographic characteristics including primary indications for surgery, history of trauma, laterality, baseline and best-corrected visual acuity (BCVA), refraction as spherical equivalent (SE), intraocular pressure (IOP), duration of follow-up, and complications were analyzed.Results: The mean preoperative BCVA was 1.38 +/- 0.46 logarithm of the minimum angle of resolution (logMAR), which improved significantly to 0.37 +/- 0.22 logMAR. The baseline refractive status measured in spherical equivalent (SE) was 4.1 +/- 6.2 Diopters (D), and the postoperative status was-0.4 +/- 0.97 D. Early postoperative complications included hypotony (n = 1; 0.57%, vitreous hemorrhage (n = 3; 1.72%), elevated IOP (n = 8; 4.59%), mild dilated pupil (n = 1; 0.57%) and corneal edema (n = 16; 9.19%). Late complications included in this study were retinal detachment (n = 1; 0.57%), cystoid macular edema (CME) (n = 1; 0.57%), primary glaucoma (n = 1; 0.57%), secondary glaucoma (n = 13; 7.47%), zonular dehiscence (n = 3; 1.72%), retinal pigment epithelium (RPE) changes (n = 3; 1.72%), choroidal coloboma (n = 2; 1.14%), posterior dislocation of posterior chamber IOL (PCIOL) (n = 1; 0.57%), corneal decompensation (n = 1; 0.57%), retinal hemorrhage (n = 1; 0.57%), macular hole (n = 1; 0.57%), chronic uveitis (n = 1; 0.57%), mild non-proliferative diabetic retinopathy (NPDR) (n = 3; 1.72%), and mild NPDR with diabetic macular edema (DME) (n = 1; 0.57%).Conclusion: Integrating IOL implantation with vitrectomy various posterior segment complications were resolved in the same setting without attempting a second surgery.

PDF - 68K, Figure legend for Supplementary Figure 1.

Abstract A monofunctional analog of sulfur mustard, 2-chloroethyl ethyl sulphide (CEES) is a well-known chemical warfare agent that induces vesicles/blisters on cutaneous toxicity in exposed individuals. However, gram-negative bacterial endotoxin lipopolysaccharide (LPS) infection with CEES exposure enhances the keratinocytes injury remains unknown. Here, we investigated the molecular mechanism of LPS infection augmented the reactive oxygen species (ROS) accumulation triggered the expression of inflammatory mediators, leading to membrane damage, disruption of cell-cell comunication and apoptosis via Erk1/2MAPK/Akt/ NF-κB pathways after CEES challenge in keratinocytes. Our results showed that LPS infection with CEES exposure increased the intracellular superoxide (O2•−), hydroxyl radical (OH·) and hydrogen peroxide (H2O2). Further, accumulated ROS activated Erk1/2MAPK, Akt, tuberin-mTOR and NF-κB in keratinocytes. The activated NF-κB stimulates inflammatory mediators, which was subsequently subdued lipids and proteins damage leading to crash the cell-cell communication and apoptosis. Protection against LPS infection with CEES toxicity could also be performed by blocking of ROS accumulation with antioxidant N-acetyl-L-cysteine (NAC) or Erk1/2MAPK or Akt inhibitors, which inhibited the intracellular redox-sensitive signaling pathways, inflammation, cell-cell communication and apoptosis. These results illustrated that accumulated ROS in keratinocyte cells function as a key NF-κB signaling pathway via Erk1/2MAPK/Akt/tuberin-mTOR regulatory signaling cascades induced by CEES exposure after LPS infection, leading to inflammation, loss of cell-cell communication and apoptosis, which was attenuated by antioxidant NAC or Erk1/2MAPK or Akt inhibitors. Moreover, the protective effects of all these inhibitors might provide the basis for the development of a therapeutic strategy to work against exposure to CEES with bacterial endotoxin infection.

Growing evidence indicates that skin injuries are a common complication of diabetes. However, the cellular and molecular mechanisms of high glucose (HG) environment trigger nitrosative stress-mediated inflammation and apoptosis in keratinocytes remains unknown. Here we investigated whether reactive nitrogen species (RNS) induced by HG environment restrain antioxidant activity, and mitochondrial dysfunction leading to inflammation, and apoptosis via stress signaling pathways in keratinocytes. Our results established that the HG environment enhanced the production of nitric oxide (NO) and peroxynitrite anion (ONOO-) by inducible NO synthase (iNOS) in keratinocytes. Overproduction of RNS in HG environment suppress the antioxidants activity leading to mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential (ΔΨm), increase in mitochondrial mass, decrease in mitochondrial transcription factor A(TFAM), increase in mitochondrial DNA (mtDNA) displacement loop (D-loop) and decrease in glycolytic flux concentration, which was attenuated by pharmacological inhibitors of NO/ONOO-, Nω-Nitro-l-argininemethyl ester hydrochloride (NAME)/hydralazine hydrochloride (Hyd.HCl). Excess production of RNS in HG environment restrained 8-oxoguanine DNA glycosylase-1 (OGG1) expression and increased 8-hydroxydeoxyguanosine (8-OHdG) accumulations in DNA were regulated by NO or ONOO-. Further, HG-induced RNA production caused an increase in the production of inflammatory mediators accompanied by activation of ERK1/2MAPK/Akt/tuberin-mTOR/IRF3 signaling cascade, lipid peroxidation (LPO), and protein carbonylation (PC) reactions followed by breakdown the cell-cell communication and apoptosis. Pre-treatment of cell with NAME/Hyd.HCl, diminished the expression of ERK1/2MAPK/Akt/tuberin-mTOR/IRF3, inflammatory mediators, and attenuated apoptosis in keratinocytes. Together, our results indicated that excess production of RNS in HG environment triggered inflammation and apoptosis, mediated by activation of ERK1/2MAPK/Akt/tuberin-mTOR/IRF3 signaling cascades in keratinocytes.

Nitrosative stress plays a critical role in retinal injury in high glucose (HG) environment of eye, but the mechanisms remain poorly understood. Here we tested the hypothesis that HG induced reactive nitrogen species (RNS) production acts as a key functional mediator of antioxidant depletion, mitochondrial dysfunction, biomolecule damage, inflammation and apoptosis. Our findings illustrated that exposure of cultured RGC-5 cells to HG significantly disrupts the antioxidant defense mechanism and mitochondrial machineries by increasing the loss of mitochondrial membrane potential (ΔѰM) and elevating mitochondrial mass. Furthermore, we used biochemical tools to analyze the changes in metabolites, sulfur amino acids (SAAs) such as L-glutathione (GSH) and L-cysteine (Cys), in the presence of HG environment. These metabolic changes were followed by an increase in glycolytic flux that is phosphofructokinase-2 (PFK-2) activity. Moreover, HG exposure results in a significant disruption of protein carbonylation (PC) and lipid peroxidation (LPO), downregulation of OGG1 and increase in 8-OHdG accumulations in RGC-5 cells. In addition, our results demonstrated that HG environment coinciding with increased expression of inflammatory mediators, cell cycle deregulation, decreased in cell viability and expression of FoxOs, increased lysosomal content leading to apoptosis. Pre-treatment of selective inhibitors of RNS significantly reduced the HG-induced cell cycle deregulation and apoptosis in RGC-5 cells. Collectively, these results illustrated that accumulated RNS exacerbates the antioxidant depletion, mitochondrial dysfunction, biomolecule damage, inflammation and apoptosis induced by HG exposure in RGC-5 cells. Treatment of pharmacological inhibitors attenuated the HG induced in retinal cells.

Reactive oxygen species (ROS) is mainly produced as a by-product from electron transport chain (ETC) of mitochondria and effectively eliminated by cellular antioxidants. However, 2-chloroethyl ethyl sulfide (CEES) exposure to keratinocytes declined antioxidant capacity and increased accumulation of ROS triggered alteration of mitochondrial activity and apoptosis is lacking. Our findings demonstrated that the electron leakage from the impaired ETC, leading to the accumulation of ROS was gradually elevating with increasing concentration of CEES exposure, which decline the activity of superoxide dismutase (SOD), manganese SOD (MnSOD) and copper-zinc SOD (Cu-ZnSOD) in keratinocytes. Further, excess accumulation of ROS, decreased the mitochondrial membrane potential (ΔΨm) and increased the mitochondrial mass with increasing dose of CEES. CEES exposure provoked the decrease in expression of transcription factor A mitochondrial (TFAM), augmented mitochondrial DNA (mtDNA) damage and altered the mtDNA-encoded oxidative phosphorylation (OXPHOS) subunits. Moreover, fragmented mtDNA translocated into cytosol, where it activated cGAS-STING and interferon regulatory factor3 (IRF3), coinciding with the increased expression of inflammatory mediators and alteration of cell-to-cell communication markers. Pre-treatment of N-acetyl-l-cysteine (NAC) or L-Nω-nitroarginine methyl ester (NAME), hydralazine hydrochloride (Hyd·HCl) or ERK1/2 or phosphoinositide3-kinase (PI3–K)/Akt inhibitors in keratinocyte cells significantly restored the CEES effect. Our findings suggest that CEES-induced mitochondrial ROS production and accumulation leads to mitochondrial dysfunction and inflammatory response in keratinocytes. However, treatment of antioxidants or ERK1/2 or PI3–K/Akt inhibitors is a novel therapeutic option for the keratinocytes complication.

Hyperglycemia and oxidative stress are the primary stressors that elicit mitochondria specific cell stress in diabetes. Here we hypothesized that elevated level of ROS in high glucose (HG) environment, trigger mitochondrial stress by damaging mitochondrial DNA (mtDNA), altering inflammatory mediators, and neurodegenerative markers via stress signalling pathway in retinal ganglion cells (RGC-5). Mechanistically, our findings illustrated that the HG environment increases the ROS production in retinal cells leading to the disruption of antioxidant defence mechanism, and altering mitochondrial machinery such as an increase in loss of mitochondrial membrane potential (ΔΨm), increase in mitochondrial mass, and increase in mtDNA fragmentation. Furthermore, fragmented mtDNA escape from mitochondria into the cytosol, where it engaged with cyclic GMP-AMP synthase (cGAS) and stimulator of IFN gene (STING) phosphorylation and activate interferon regulatory factor 3 (IRF3) via ERK1/2-Akt-tuberin-mTOR dependent pathways. Our results further indicate that siRNA-mediated gene silencing of tuberin suppresses the strong downregulation of tuberin-mTOR-IRF3 activation. HG environment resulted in activation of IRF3, coinciding with the increased expression of inflammatory mediators and neurodegenerative markers. Pre-treatment of N-acetyl-l-cysteine (NAC) or ERK1/2 or phosphoinositide3-kinase (PI3-K)/Akt inhibitors in RGC-5 cells significantly reduced the HG-induced IRF3 expression and declined the expression of neurodegenerative markers. Collectively, our results demonstrates that HG-induced over production of ROS, disrupts the antioxidant defence mechanism and mitochondrial dysfunction, leading to alterations of inflammatory mediators and neurodegenerative markers through the ERK1/2-Akt-tuberin-mTOR dependent signalling pathway in RGC-5 cells.

Mitochondria are fascinating structures of the cellular compartments that generate energy to run the cells. However, inherent disorders of mitochondria due to diabetes can cause major disruption of metabolism that produces huge amount of reactive oxygen species (ROS). Here we study the elevated level of ROS provoked by high glucose (HG) environment triggered mitochondrial dysfunction, inflammatory response and apoptosis via stress signalling pathway in keratinocytes. Our results demonstrated that elevated glucose level in keratinoctes, increase the accumulations of ROS and decrease in cellular antioxidant capacities. Moreover, excess production of ROS was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential (ΔΨm), increase in mitochondrial mass, alteration of mitochondrial respiratory complexes, cytochrome c (Cyt c) release, decrease in mitochondrial transcription factor A (TFAM) and increase in mitochondrial DNA (mtDNA) fragmentation. Damaged mtDNA escaped into the cytosol, where it engaged the activation of ERK1/2, PI3K/Akt, tuberin and mTOR via cGAS-STING leading to IRF3 activation. Pre-treatment of pharmacological inhibitors, ERK1/2 or PI3K/Akt suppressed the IRF3 activation. Furthermore, our results demonstrated that activation of IRF3 in HG environment coinciding with increased expression of inflammatory mediators. Excess production of ROS interfered with decreased in cell viability, increased lysosomal content and expression of FoxOs, leading to cell cycle deregulation and apoptosis. Pre-treatment of N-acetyl-l-cysteine (NAC) significantly reduced the HG-induced cell cycle deregulation and apoptosis in keratinocytes. In conclusion, increased oxidative stress underlies the decrease in antioxidant capacities and mitochondrial dysfunction in HG environment correlate with inflammation response and apoptosis via ERK1/2-PI3K/Akt-IRF3 pathway in keratinoctes.

Myxovirus resistance (Mx) proteins represents the subclass of the dynamin superfamily of large Guanosine triphosphates (GTPases), play esential role in intracellular vesicle trafficking, endocytosis, organelle homeostasis and mitochondria distribution. These proteins are key players of the vertebrate immune system, induced by type-I and type-III interferons (IFN) of infected host and inhibit viral replication by sequestering its nucleoprotein. In the present study, we report the sequencing and characterization of Cirrhinus mrigala Mx protein (CmMx) for the first time and observed its constitutive expression in different tissues for a period of fourteen days. The synthetic peptide, LSGVALPRGTGI, was dissolved in PBS and injected into a rabbit and the antibody raised against CmMx was used to study the level of its expression. The full length of the CmMx cDNA is 2244 bp with a molecular mass of 70.9 kDa and a predicted isoelectric point of 8.25. The 627 amino acids polypeptide formed of three main functional domains: N-terminal GTPase domain (GD), a middle domain (MD) and GTPase effector domain (GED) with carboxy terminal leucine zipper motif. The 3D models of CmMx protein was modeled based on available close structural homologs and further validated through molecular dynamics (MD) simulations. MD study revealed the importance of G-domain responsible for recognition of GTP, which perfectly corroborate with earlier studies. MM/PBSA binding free energy analysis displayed that van der Waals and electrostatic energy were the key driving force behind molecular recognition of GTP by CmMx protein. The results from this study will illuminate more lights into the ongoing research on myxovirus resistance protein and its role in inhibition of viral replication in other eukaryotic system as well.

2-Chloroethyl ethyl sulfide (CEES) is a well-known chemical warfare agent that induces cellular stress in exposed individuals. However, molecular mechanisms of CEES-induced oxidative stress–mediated metabolic deregulation are not clearly elucidated. Here we investigated CEES-induced free radical production act as key functional mediators of metabolic stress via Erk1/2 mitogen–activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase (PI3K/Akt) signaling cascades in keratinocytes. We observed that CEES exposure disrupts the cellular antioxidant defense capacities leading to increase in free oxygen and nitrogen radical accumulation in keratinocytes. These unusual cellular abnormalities initiate cellular stress via Erk1/2-PI3K/Akt signaling pathways. Biochemical tools were used to analyze the changes in metabolites including sulfur amino acids (SAAs), namely, l-glutathione (GSH) and l-cysteine (Cys), in the presence of selective inhibitors of reactive oxygen/nitrogen species (ROS/RNS), Erk1/2, or PI3K/Akt after CEES exposure. Importantly, these metabolite changes were accompanied by a decrease in the glycolytic flux, consistent with the observed decrease in 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) concentration and these CEES-induced phenomena were attenuated by pretreatment of Erk1/2 or PI3-K/Akt inhibitors. On the other hand, CEES exposure disrupts the protein carbonylation (PC) and lipid peroxidation (LPO) in keratinocytes leading to inflammation, crash of the cell–cell communication, cell cycle deregulation, and apoptosis via Erk1/2-PI3K/Akt pathways. However, pretreatment of Erk1/2 or PI3K/Akt inhibitors attenuated the CEES action. Collectively, these results illustrated that accumulated free radicals act as key functional mediators for inflammation, and apoptosis via Erk1/2-PI3K/Akt regulatory signaling cascades induced by CEES exposure. Treatment of pharmacological Erk1/2-PI3K/Akt inhibitors attenuated the CEES-induced keratinocyte injury that may provide the basis for the development of therapeutic strategy to work against CEES exposure.

PURPOSE:Childhood ocular morbidity involves a spectrum of eye diseases that critically impact the mental development, future education and quality of life. However, there is limited evidence about the early detection and appropriate treatment of ocular morbidity in children <20 years. This study was aimed to assess the prevalence and make a comparison between the different types of ocular morbidity in children of both sexes in the age group of 6-17 years in the eastern India.METHODS:A cross-sectional survey of ocular morbidity among children <17 years of age who presented at the Department of Ophthalmology, Kalinga Institute of Medical Sciences, Bhubaneswar, and Vision Care Center for Retina, Bhubaneswar, in the eastern India between January 2015 and March 2018 was accomplished. Demographic information, visual acuity, type of eye injury, refractive errors and other detailed ophthalmic examination were screened.RESULTS:A total of 633 children (age 6-17 years) were examined in this study. The majority of cases were observed in children of age 12-17 years, accounting for almost close to half of all the cases. The prevalence of ocular morbidity was 45.92% in males and 53.97% in females. The most common ocular morbidity in children encountered was refractive error (54.62%), followed by congenital abnormalities (9%), allergic conjunctivitis (8.52%) and traumatic eye injury (7.1%). There was an increase in ocular morbidity with age, especially the refractive error and congenital abnormalities.CONCLUSION:A large number of ocular morbidity was observed in children of age <17 years. Since most of this morbidity was preventable or treatable, reasonable service for ocular morbidity and early age screening are effective methods to reduce this load. Moreover, health education for the prevention of childhood ocular morbidity and, at the same time, early presentation of children to ophthalmic hospitals for the treatment of eye disorders are essential.

BACKGROUND:The phenotypic expression of sickle cell disease (SCD) is a complex pathophysiologic condition. However, sickle erythrocytes might be the cause for multiple sources of pro-oxidant processes with consequent linked to chronic and systemic oxidative stress. Herein, we explored the SCD phenomena could be the result in formation of oxidative stress as well as inflammation in children. MATERIAL AND METHODS:Blood samples of 147 SCD subjects were evaluated. A control group was formed of 156 individuals without SCD. Different oxidative stress markers and inflammatory mediators were measured by using various biochemical techniques. Plasma samples were collected from blood for the measurement of antioxidants and reactive oxygen species (ROS). RESULTS:The levels of plasma hydroxyl radical (HO•), and nitric oxide (NO) production were higher in SCD children in compared to control groups. The plasma antioxidants capacities such as superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx) and protein thiol levels were significantly reduced in SCD children. The plasma lipid peroxidation, protein carbonylation, DNA damage markers were significantly altered in different age groups of SCD children. Further, our results showed that SCD children have chronic inflammatory disease due to persistent alteration of haemoglobin content, reticulocyte, total bilirubin, platelet, creatinine, leukocytes, and altered expression of inflammatory mediators in compared to control groups. CONCLUSION:SCD children have high oxidative stress, and conversely, decreased antioxidant activity. Decrease in antioxidant activity might explained the reduction in lipid peroxidation, protein carbonylation and increased inflammation, which in turn intensify the symptoms of SCD in children.