ABSTRACT
Monoclonal antibodies (mAb) and other biological drugs are affected by enzymatic polysorbate (PS) degradation that reduces product stability and jeopardizes the supply of innovative medicines. PS represents a critical surfactant stabilizing the active pharmaceutical ingredients, which are produced by recombinant Chinese hamster ovary (CHO) cell lines. While the list of potential PS-degrading CHO host cell proteins (HCPs) has grown over the years, tangible data on industrially relevant HCPs are still scarce. By means of a highly sensitive liquid chromatography-tandem mass spectrometry method, we investigated seven different mAb products, resulting in the identification of 12 potentially PS-degrading hydrolases, including the strongly PS-degrading lipoprotein lipase (LPL). Using an LPL knockout CHO host cell line, we were able to stably overexpress and purify the remaining candidate hydrolases through orthogonal affinity chromatography methods, enabling their detailed functional characterization. Applying a PS degradation assay, we found nine mostly secreted, PS-active hydrolases with varying hydrolytic activity. All active hydrolases showed a serine-histidine-aspartate/glutamate catalytical triad. Further, we subjected the active hydrolases to pH-screenings and revealed a diverse range of activity optima, which can facilitate the identification of residual hydrolases during bioprocess development. Ultimately, we compiled our dataset in a risk matrix identifying PAF-AH, LIPA, PPT1, and LPLA2 as highly critical hydrolases based on their cellular expression, detection in purified antibodies, active secretion, and PS degradation activity. With this work, we pave the way toward a comprehensive functional characterization of PS-degrading hydrolases and provide a basis for a future reduction of PS degradation in biopharmaceutical drug products.
Subject(s)
Antibodies, Monoclonal , Cricetulus , Hydrolases , CHO Cells , Animals , Antibodies, Monoclonal/chemistry , Hydrolases/metabolism , Polysorbates/chemistry , Biological Products/metabolism , HumansABSTRACT
BACKGROUND AND OBJECTIVES: To systematically describe the clinical picture of double-antibody seronegative neuromyelitis optica spectrum disorders (DN-NMOSD) with specific emphasis on retinal involvement. METHODS: Cross-sectional data of 25 people with DN-NMOSD (48 eyes) with and without a history of optic neuritis (ON) were included in this study along with data from 25 people with aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorder (AQP4-NMOSD, 46 eyes) and from 25 healthy controls (HCs, 49 eyes) for comparison. All groups were matched for age and sex and included from the collaborative retrospective study of retinal optical coherence tomography (OCT) in neuromyelitis optica (CROCTINO). Participants underwent OCT with central postprocessing and local neurologic examination and antibody testing. Retinal neurodegeneration was quantified as peripapillary retinal nerve fiber layer thickness (pRNFL) and combined ganglion cell and inner plexiform layer thickness (GCIPL). RESULTS: This DN-NMOSD cohort had a history of [median (inter-quartile range)] 6 (5; 9) attacks within their 5 ± 4 years since onset. Myelitis and ON were the most common attack types. In DN-NMOSD eyes after ON, pRNFL (p < 0.001) and GCIPL (p = 0.023) were thinner compared with eyes of HCs. Even after only one ON episode, DN-NMOSD eyes already had considerable neuroaxonal loss compared with HCs. In DN-NMOSD eyes without a history of ON, pRNFL (p = 0.027) and GCIPL (p = 0.022) were also reduced compared with eyes of HCs. However, there was no difference in pRNFL and GCIPL between DN-NMOSD and AQP4-NMOSD for the whole group and for subsets with a history of ON and without a history of ON-as well as between variances of retinal layer thicknesses. DISCUSSION: DN-NMOSD is characterized by severe retinal damage after ON and attack-independent retinal neurodegeneration. Most of the damage occurs during the first ON episode, which highlights the need for better diagnostic markers in DN-NMOSD to facilitate an earlier diagnosis as well as for effective and early treatments. In this study, people with DN-NMOSD presented with homogeneous clinical and imaging findings potentially suggesting a common retinal pathology in these patients.
Subject(s)
Aquaporin 4 , Neuromyelitis Optica , Tomography, Optical Coherence , Humans , Neuromyelitis Optica/diagnostic imaging , Neuromyelitis Optica/immunology , Neuromyelitis Optica/blood , Female , Male , Adult , Cross-Sectional Studies , Middle Aged , Aquaporin 4/immunology , Retrospective Studies , Autoantibodies/blood , Retina/diagnostic imaging , Retina/pathology , Retina/immunologyABSTRACT
Introduction: One of the main causes of acquired blindness and impairment in children is ocular trauma. This study aimed to evaluate the epidemiological and clinical characteristics of pediatric patients hospitalized with open globe injuries (OGI). Methods: A retrospective cross-sectional study was conducted on children diagnosed with OGI at a referral Hospital affiliated with Isfahan University of Medical Sciences, Isfahan, Iran, from 2014 to 2018. Results: 375 OGI medical records were detected during the study period. The common culprits for OGI in boys were knives (21.3%), wood (19.7%), metal bodies (12.2%), and glass (11.8%). In girls, the common causes were knives (28.7%), glass (24.3%), pencils (11.3%), and wood (10.4%). Boys had a greater rate of Intraocular foreign body (IOFB) (p= 0.052) but had lower odds of blindness compared to girls (OR=0.48; 95% CI: (0.24, 0.98); p = 0.04). Patients with corneal lacerations had lower chances of long-term admission than those with corneal and scleral lacerations (OR= 0.35, 95% CI: (0.17, 0.69); p = 0.02). Conclusion: Most pediatric OGIs occur in boys. knives were the principal culprit for OGI, followed by glass and wood. Boys had a greater IOFB rate but lower blindness odds than girls.
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Purpose: This study aimed to compare and quantify the ganglion cell complex (GCC), macular thickness, and vessel density (VD) in amblyopic eyes and their corresponding fellow eyes using optical coherence tomography angiography (OCTA). Methods: This cross-sectional study analyzed 32 unilateral amblyopic patients, examining both of their eyes. The study assessed parameters such as GCC thickness, macular thickness (total, inner, and outer layers), and VD in the optic nerve and macular region using spectral-domain OCTA. Results: This study analyzed data from 30 unilateral amblyopic patients with a mean age of 28.7 ± 18.3 years. Amblyopic eyes had lower mean best-corrected visual acuity compared with healthy eyes. However, no significant differences were found in retinal nerve fiber layer (RNFL) thickness, GCC thickness, and overall retinal thickness between amblyopic and fellow eyes when accounting for factors such as axial length and signal strength index. In patients older than 30 years, amblyopic eyes had a higher global loss volume (GLV) compared with fellow eyes (p = 0.02). In addition, blood VD within the optic disc and superficial/deep capillary plexuses in different macular regions were significantly lower in amblyopic eyes compared with fellow eyes. Conclusions: This study found significant differences in VD and the GLV index between amblyopic eyes and healthy eyes, particularly in older patients. However, there were no notable differences in macular thickness and RNFL thickness. Further research is needed to determine the clinical relevance of these findings.
Subject(s)
Angiography , Tomography, Optical Coherence , Humans , Aged , Child , Adolescent , Young Adult , Adult , Middle Aged , Cross-Sectional StudiesABSTRACT
Host cell proteins (HCPs) are process-related impurities that can negatively impact the quality of biotherapeutics. Some HCPs possess enzymatic activity and can affect the active pharmaceutical ingredient (API) or excipients such as polysorbates (PS). PSs are a class of non-ionic surfactants commonly used as excipients in biotherapeutics to enhance the stability of APIs. The enzyme activity of certain HCPs can result in the degradation of PSs, leading to particle formation and decreased shelf life of biotherapeutics. Identifying and characterizing these HCPs is therefore crucial. This study employed the Activity-Based Protein Profiling (ABPP) technique to investigate the effect of pH on the activity of HCPs that have the potential to degrade polysorbates. Two probes were utilized: the commercially available fluorophosphonate (FP)-Desthiobiotin probe and a probe based on the antiobesity drug, Orlistat. Over 50 HCPs were identified, showing a strong dependence on pH-milieu regarding their enzyme activity. These findings underscore the importance of accounting for pH variations in the ABPP method and other investigations of HCP activity. Notably, the Orlistat-based probe (OBP) enabled us to investigate the enzymatic activity of a wider range of HCPs, emphasizing the advantage of using more than one probe for ABPP. Finally, this study led to the discovery of previously unreported active enzymes, including three HCPs from the carboxylesterase enzyme family.
Subject(s)
Excipients , Polysorbates , Polysorbates/chemistry , Excipients/chemistry , Antibodies, Monoclonal/chemistry , Orlistat , Mass Spectrometry/methods , Hydrogen-Ion ConcentrationABSTRACT
PURPOSE: To systematically review the published manuscripts on the non-steroidal intravitreal injection for treatment of noninfectious uveitic cystoid macular edema (CME). METHODS: The PubMed, Scopus, and Web of Science, Science Direct, ProQuest, Cochrane Library, ProQuest, Embase, Clinical Key, and Springer were searched for relevant articles published until May 2022. The random-effects models were used to estimate the mean difference (MD) and 95% confidence interval (CI) for postoperative central macular thickness (CMT) and visual acuity (VA) changes. VA was transformed into the logarithm of the minimum angle of resolution (LogMAR). Meta-regression was conducted for adjusting the effects of potential confounders. RESULTS: A total of 17 relevant studies (258 eyes) were included in this meta-analysis. A significant improvement was observed in CMT in the last follow up (350.89 ± 108.43) compared to the baseline (452.3 ± 112.67) (Log MD = 1.82, 95% CI = 1.62, 2.02; I2 = 57.7%; P = 0.002). Additionally, VA also significantly improved in the last follow up (0.56 ± 0.29) compared to the baseline (0.75 ± 0.3) (Exponential MD = 0.82, 95% CI = 0.69, 0.95; I2 = 0.0%; P = 0.98). The subgroups analyzed included ten studies on anti-vascular endothelial growth factors (VEGF), three studies on infliximab, two studies on methotrexate (MTX), and two studies on diclofenac. All subgroups showed a significant improvement in both CMT and VA at the last follow-up (P < 0.05). CONCLUSION: Non-steroidal intravitreal injection including bevacizumab, ranibizumab, infliximab, MTX and diclofenac appears to be an effective treatment option for noninfectious uveitic CME.
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Oligodendrocytes are generated via a two-step mechanism from pluripotent neural stem cells (NSCs): after differentiation of NSCs to oligodendrocyte precursor/NG2 cells (OPCs), they further develop into mature oligodendrocytes. The first step of this differentiation process is only incompletely understood. In this study, we utilized the neurosphere assay to investigate NSC to OPC differentiation in a time course-dependent manner by mass spectrometry-based (phospho-) proteomics. We identify doublecortin-like kinase 1 (Dclk1) as one of the most prominently regulated proteins in both datasets, and show that it undergoes a gradual transition between its short/long isoform during NSC to OPC differentiation. This is regulated by phosphorylation of its SP-rich region, resulting in inhibition of proteolytic Dclk1 long cleavage, and therefore Dclk1 short generation. Through interactome analyses of different Dclk1 isoforms by proximity biotinylation, we characterize their individual putative interaction partners and substrates. All data are available via ProteomeXchange with identifier PXD040652.
Subject(s)
Neural Stem Cells , Oligodendrocyte Precursor Cells , Cell Differentiation , Doublecortin-Like Kinases , Oligodendroglia , Phosphorylation , Protein Serine-Threonine Kinases , ProteomicsABSTRACT
BACKGROUND: The therapeutic profile of the patients with rheumatoid arthritis (RA) commonly consists of immunosuppressive and anti-inflammatory compounds. Here in this research, we assessed the potential effect of drug treatment in the RA patients in increasing the risk of coronavirus disease 2019 (COVID-19) infection. METHODS: In this retrospective cross-sectional study, 200 subjects with RA were recruited. The treatment profile of the subjects for the past 6 months was collected. The COVID-19 diagnosis was implemented based on the standard molecular tests and clinical examinations. Serum concentration of cytokines was measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: It was detected that there was an increased risk of COVID-19 in RA subjects receiving Etanercept (OR = 3.51, 95% CI 1.19-10.30, P = 0.022). Concentrations of Interleukin (IL)-1ß, Interferon (IFN)-γ, Tumor necrosis factor (TNF)-α, IL-6, IL-17A, and IL-23 were significantly higher in the RA patients with COVID-19 relative to RA cases without COVID-19. In RA/COVID-19 cases receiving Etanercept, serum levels of TNF-α, IL-1ß, and IL-6 were significantly lower than RA/COVID-19 subjects without Etanercept therapy. CONCLUSIONS: It seems that Etanercept therapy in RA cases might increase proneness of the COVID-19 risk in these cases. The mechanism of this increased risk may stem from suppressing a protective immunity state in the RA cases.
Subject(s)
Arthritis, Rheumatoid , COVID-19 , Humans , Etanercept/therapeutic use , Inflammation Mediators/analysis , Interleukin-6 , Retrospective Studies , Cross-Sectional Studies , COVID-19 Testing , Cytokines , Tumor Necrosis Factor-alphaABSTRACT
PURPOSE: To investigate the effect of oral isotretinoin therapy on central macular thickness (CMT) thickness and choroidal thickness (CT) using optical coherence tomography (OCT). METHODS: CT and CMT thickness of 43 eyes were evaluated at baseline, the third, and sixth month of isotretinoin therapy by spectral-domain OCT. For assessment of CT, OCT measurements were obtained at the fovea with six additional measurements at adjacent locations (at 500-1000 µm temporal to the fovea and 500-1000 µm nasal to the fovea). RESULTS: Forty-three eyes from 43 patients with acne vulgaris, including 33 females (76.7%), who had a mean age of 24.81 ± 6.60 years, completed the study. The mean CMT was 231.49 ± 19.52 at the baseline and significantly decreased to 229.0 ± 19.57 (p = 0.02) and 229.28 ± 18.83 after three and six months, respectively (p < 0.03). The change in the macular thicknesses measured at four quadrants and choroidal thicknesses were not statistically significant during the study (p > 0.05). CONCLUSION: The result of our study demonstrated choroidal thickness change is not significant in patients with acne vulgaris after systemic isotretinoin therapy during six months of follow-up. The decreased CMT amount was 2.2 microns; even if statistically significant, this amount is clinically insignificant.
Subject(s)
Acne Vulgaris , Isotretinoin , Female , Humans , Adolescent , Young Adult , Adult , Isotretinoin/adverse effects , Acne Vulgaris/drug therapy , Choroid/diagnostic imaging , Fovea Centralis , Tomography, Optical Coherence/methodsABSTRACT
Objective: Curcumin is a safe phytochemical with antioxidant, anti-inflammatory, antidiabetic, and lipid-lowering effects. This study aims to investigate the efficacy of curcumin-piperine in non-proliferative diabetic retinopathy. Materials and Methods: In this double-blind randomized trial, 60 diabetic retinopathy patients after meeting the inclusion criteria will be randomly assigned to two groups of curcumin-piperine supplementation (1000 mg per day for 12 weeks) or receiving placebo. The density of small blood vessels in the retina by optical coherence tomography angiography (OCTA), fasting blood glucose, triglyceride, renal indices (blood urea nitrogen and creatinine), high-sensitivity C-reactive protein, total antioxidant capacity, total oxidant status, body mass index, waist circumference, and weight will be measured. Conclusion: If the beneficial effects of curcumin on diabetic retinopathy are observed, this safe, this natural and inexpensive herbal supplement can be considered a therapeutic solution in these patients.
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BACKGROUND: The novel optic neuritis (ON) diagnostic criteria include intereye differences (IED) of optical coherence tomography (OCT) parameters. IED has proven valuable for ON diagnosis in multiple sclerosis but has not been evaluated in aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4+NMOSD). We evaluated the diagnostic accuracy of intereye absolute (IEAD) and percentage difference (IEPD) in AQP4+NMOSD after unilateral ON >6 months before OCT as compared with healthy controls (HC). METHODS: Twenty-eight AQP4+NMOSD after unilateral ON (NMOSD-ON), 62 HC and 45 AQP4+NMOSD without ON history (NMOSD-NON) were recruited by 13 centres as part of the international Collaborative Retrospective Study on retinal OCT in Neuromyelitis Optica study. Mean thickness of peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell and inner plexiform layer (GCIPL) were quantified by Spectralis spectral domain OCT. Threshold values of the ON diagnostic criteria (pRNFL: IEAD 5 µm, IEPD 5%; GCIPL: IEAD: 4 µm, IEPD: 4%) were evaluated using receiver operating characteristics and area under the curve (AUC) metrics. RESULTS: The discriminative power was high for NMOSD-ON versus HC for IEAD (pRNFL: AUC 0.95, specificity 82%, sensitivity 86%; GCIPL: AUC 0.93, specificity 98%, sensitivity 75%) and IEPD (pRNFL: AUC 0.96, specificity 87%, sensitivity 89%; GCIPL: AUC 0.94, specificity 96%, sensitivity 82%). The discriminative power was high/moderate for NMOSD-ON versus NMOSD-NON for IEAD (pRNFL: AUC 0.92, specificity 77%, sensitivity 86%; GCIP: AUC 0.87, specificity 85%, sensitivity 75%) and for IEPD (pRNFL: AUC 0.94, specificity 82%, sensitivity 89%; GCIP: AUC 0.88, specificity 82%, sensitivity 82%). CONCLUSIONS: Results support the validation of the IED metrics as OCT parameters of the novel diagnostic ON criteria in AQP4+NMOSD.
Subject(s)
Aquaporins , Neuromyelitis Optica , Optic Neuritis , Humans , Neuromyelitis Optica/diagnosis , Retrospective Studies , Benchmarking , Optic Neuritis/diagnosis , Tomography, Optical Coherence/methods , Autoantibodies , Aquaporin 4ABSTRACT
OBJECTIVE: The aim of the study is to determine characteristic features of open globe injuries caused by firecrackers among pediatric population. METHODS: In this retrospective cross-sectional chart review, medical records of children with ocular trauma who were hospitalized in Isfahan, Iran, during 2013-2017 were reviewed. We analyzed the collected data before and after propensity score (PS) matching. RESULTS: Of 396 pediatric patients with open globe injury, 22 injuries (5.9%) were caused by firecrackers. Hyphema, iris prolapse, and lens rupture were noted in 15 (68.18%), 10 (45.45%), and 2 (9.09) eyes, respectively. None of patients had endophthalmitis. The mean age of patients in firecracker group was higher and significant (11.86 ± 4.05 in firecracker vs 7.80 ± 4.68 in nonfirecracker, P < 0.001). Furthermore, most boys were in firecracker group (95.5%, P = 0.005). Patients in firecracker group resided more in urban areas (86.4%, P = 0.054) and had more intraocular foreign body (IOFB) in the eyes (40.9%, P < 0.001). After PS matching, patients in firecracker group had higher IOFB ( P = 0.008). In logistic regression models, patients with corneal lacerations had lower odds for long-time admission (≥4 days) than patients with both corneal and scleral lacerations in crude model (odds ratio, 0.35; 95% confidence interval, 0.17-0.69) and adjusted model (odds ratio, 0.37; 95% CI, 0.18 to 0.74). After PS matching, there was no significant association between risk factors and outcomes. CONCLUSIONS: The present study showed several differences between the pediatric open globe injuries caused by firecrackers and other mechanisms of injuries, including the age, sex, living place, presence of IOFB, and length of hospital stay.
Subject(s)
Eye Foreign Bodies , Eye Injuries, Penetrating , Eye Injuries , Lacerations , Multiple Trauma , Male , Child , Humans , Lacerations/complications , Retrospective Studies , Iran/epidemiology , Cross-Sectional Studies , Eye Injuries, Penetrating/complications , Eye Injuries, Penetrating/epidemiology , Eye Injuries/epidemiology , Eye Injuries/etiology , Eye Foreign Bodies/epidemiology , Eye Foreign Bodies/etiology , HospitalsABSTRACT
BACKGROUND: To investigate the possible association of different pattern of diabetic retinopathy (DR) on corneal endothelium cells in type 2 diabetes mellitus patients. METHODS: In this descriptive-analytical cross-sectional study, corneal endothelium parameters including endothelial cell density (ECD), average cell size (AVG), coefficient of variation in cell size (CV), and hexagonality (Hex) were evaluated by non-contact specular microscopy. RESULTS: One hundred and thirty-four eyes of 134 diabetic patients including 77 females (57.5%) with a mean age of 61.03 ± 8.08 years were enrolled. The overall corneal parameters in diabetic patients with and without retinopathy were not significantly different (P > 0.05). There is a significant relationship between CV and the duration of the disease with age variable control (B = 0.369, p-value < 0.001). CONCLUSIONS: Corneal endothelial parameters were not associated with DM in patients without and with DR. There is a significant relationship between CV and the duration of the disease with age variable control.
Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Retinopathy , Female , Humans , Middle Aged , Aged , Endothelium, Corneal , Cross-Sectional Studies , Diabetes Mellitus, Type 2/complications , Cell CountABSTRACT
This study was meant to describe a Poloxamer hydrogel combining Chitosan-N-acetyl-L-cysteine (CNAC) nanoparticles to increase loading and sustained intravitreal administration of Avastin macromolecule. To increase the drug's efficacy and reduce the interfacial fluid pressure in a formulation, dexamethasone was used. To do so, CNAC was synthesized. Then, Avastin- loaded CNAC nanoparticles were prepared and optimized. The resulting hydrogel's sol-gel transition time and viscosity were determined using poloxamer and hydroxypropylmethylcellulose (HPMC). In vitro and in vivo investigations of Avastin-loaded CNAC nanoparticles and hydrogel comprising dexamethasone/Avastin-loaded CNAC nanoparticles were determined. In vitro, the drug release profile of optimized hydrogel containing Avastin-loaded CNAC nanoparticles was sustained and controlled over 256 h. The obtained results point to poloxamer/HPMC (18 %/0.5 %) as the best formulations for this hydrogel to develop a sol-gel transition. About 97 % of dexamethasone was released from the hydrogel within 18 h. In vivo results indicated that the optimized formulation compared with free Avastin could improve Diabetic retinopathy (DR). Consequently, we infer that this new drug delivery method may enhance Avastin intravitreal administration, lowering the frequency, danger, and expense of heavy intravitreal injections and resulting in improved treatment of posterior eye segment neovascularization and concomitant vitreoretinal disorders.
Subject(s)
Chitosan , Nanoparticles , Acetylcysteine , Bevacizumab/pharmacology , Chitosan/chemistry , Dexamethasone/pharmacology , Hydrogels/chemistry , Hypromellose Derivatives , Nanoparticles/chemistry , Poloxamer/chemistryABSTRACT
OBJECTIVE: Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. This study aimed to compare the effect of sunitinib-loaded poly (glycerol sebacate) (PGS)/gelatin nanoparticles doped in an injectable hydrogel with bevacizumab as a standard treatment of DR. METHODS: The shear-sensitive hydrogel was prepared based on tragacanthic acid (TA) cross-linked with sodium acetate. DR was induced in rats by streptozotocin (STZ), and the animals were injected intravitreally a single dose of 20 µL sunitinib solution in three different concentrations (12.5, 25, and 50 µg/mL), sunitinib-loaded nanoparticles in hydrogel (413 µg/mL) and bevacizumab solution (6.25 mg/mL). The efficacy of the treatments was studied by histological and immunohisitological tests, angiogenesis, and optical coherence tomography (OCT). Vascular endothelial growth factor (VEGF) concentration was measured in the retina. RESULTS: The results revealed that 20 µL of sunitinib with the concentration of 25 µg/mL was effective in DR without any disruption in the retina or any other side effects. This dose was considered the therapeutic dose for nanoparticles. Sunitinib loaded PGS/gelatin nanoparticles that were incorporated in the injectable hydrogel were as effective as bevacizumab in controlling DR. Although sunitinib solution reduced VEGF production and neovascularization in the retina compared to the negative control group, it was not as suitable as the nanoparticles. TA-based hydrogel showed no toxicity on the normal retina, and the angiography and histologic studies confirmed the VEGF results.' CONCLUSIONS: Sunitinib nanoparticles doped in TA hydrogel may be an appropriate substitution of bevacizumab in the treatment of DR.
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Nanoparticles , Animals , Bevacizumab/therapeutic use , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Gelatin , Hydrogels , Rats , Sunitinib/therapeutic use , Vascular Endothelial Growth Factor A/metabolismABSTRACT
AIMS: The degeneration of retinal neurons which occurs in many neurodegenerative diseases of retina such as retinitis pigmentosa and aged-related macular degeneration, is a progressive phenomenon and leads to permanent visual disability. Aside from their economic and social impact, those who suffer from these diseases have a poor quality of life due to the lack of cures. Researchers have turned to stem cell therapies as a potential solution to this global health crisis. Mesenchymal stem cells (MSCs) and their paracrine agents such as conditioned medium (CM) and exosomes (Exo) have been applied to treat different retinal disorders. This study compared the therapeutic effects of human adipose mesenchymal stem cells (hADSCs) and their secretome on an in vivo model of sodium iodate retinal neurodegeneration. MAIN METHODS: We analyzed the expression of retinal cells' specific mRNAs by RT-PCR and proteins by immunostaining as well as performing visual cliff avoidance test as a functional evaluation technique. There were four therapeutic groups in this study: hADSC, hADSC-CM, hADSC-Exo and hADSC-Exo + CM. KEY FINDINGS: Although all groups showed different therapeutic effects on various retinal cells, the results of hADSC-CM were most striking, especially in terms of photoreceptor regeneration and retinal function. SIGNIFICANCE: The findings of present study demonstrated the different effects of MSC-based therapies on various retinal cells which could be helpful in designing more precise treatments that suit to each neurodegenerative disease mechanism and the cells involved. It also suggests that CM might be a better choice due to its multifactorial characteristic.
Subject(s)
Mesenchymal Stem Cells , Neurodegenerative Diseases , Retinal Degeneration , Aged , Animals , Culture Media, Conditioned/metabolism , Culture Media, Conditioned/pharmacology , Humans , Iodates , Mesenchymal Stem Cells/metabolism , Neurodegenerative Diseases/metabolism , Quality of Life , Rats , Retinal Degeneration/chemically induced , Retinal Degeneration/metabolism , Retinal Degeneration/therapyABSTRACT
The current report is a rare case of paracentral acute middle maculopathy (PAMM) in a previously healthy man following COVID-19 vaccination.
ABSTRACT
PURPOSE: The aim of this study was to evaluate the ocular disorders in COVID-19 patients, two to three months after infection. METHODS: In this cross-sectional, historically controlled study, fifty-one COVID-19 patients were compared with thirty-seven age, and gender-matched healthy individuals. After complete ophthalmological examination, all participants underwent peripapillary and macular optical coherence tomography, and optical coherence tomography angiography (OCTA) measurements (OptoVue Inc, Freemont, CA, USA). RESULTS: The time between the initial onset of symptoms, and ophthalmologic examination was 63.31±15.21 (40-95 days). Ophthalmic examination of all the recovered COVID-19 patients was within normal range. None of the peripapillary and macular OCTA parameters were significantly different between the two groups with pairwise comparisons, but after adjusting for age, gender, axial length, and signal strength index (SSI), recovered COVID-19 eyes showed a significant increase in peripapillary retinal nerve fiber (RNFL) thickness, superficial, and deep macular vessel densities in parafoveal and perifoveal regions compared with healthy control eyes (p<= 0.05). Inner retinal thickness overall is higher in recovered COVID-19 eyes compared to healthy eyes after adjustment. CONCLUSION: Patients with moderate-intensity SARS-CoV-2 pneumonia had altered peripapillary and macular vessel density compared to healthy subjects. Further investigation is warranted to analyze the correlation of these changes with disease severity as well as evolution of these changes over time.
Subject(s)
COVID-19 , Optic Disk , Photochemotherapy , Cross-Sectional Studies , Fluorescein Angiography , Humans , Photochemotherapy/methods , Retinal Vessels/diagnostic imaging , SARS-CoV-2 , Tomography, Optical Coherence/methodsABSTRACT
Nowadays, retinal optical coherence tomography (OCT) plays an important role in ophthalmology and automatic analysis of the OCT is of real importance: image denoising facilitates a better diagnosis and image segmentation and classification are undeniably critical in treatment evaluation. Synthetic OCT was recently considered to provide a benchmark for quantitative comparison of automatic algorithms and to be utilized in the training stage of novel solutions based on deep learning. Due to complicated data structure in retinal OCTs, a limited number of delineated OCT datasets are already available in presence of abnormalities; furthermore, the intrinsic three-dimensional (3D) structure of OCT is ignored in many public 2D datasets. We propose a new synthetic method, applicable to 3D data and feasible in presence of abnormalities like diabetic macular edema (DME). In this method, a limited number of OCT data is used during the training step and the Active Shape Model is used to produce synthetic OCTs plus delineation of retinal boundaries and location of abnormalities. Statistical comparison of thickness maps showed that synthetic dataset can be used as a statistically acceptable representative of the original dataset (p > 0.05). Visual inspection of the synthesized vessels was also promising. Regarding the texture features of the synthesized datasets, Q-Q plots were used, and even in cases that the points have slightly digressed from the straight line, the p-values of the Kolmogorov-Smirnov test rejected the null hypothesis and showed the same distribution in texture features of the real and the synthetic data. The proposed algorithm provides a unique benchmark for comparison of OCT enhancement methods and a tailored augmentation method to overcome the limited number of OCTs in deep learning algorithms.
Subject(s)
Diabetic Retinopathy , Macular Edema , Algorithms , Diabetic Retinopathy/diagnostic imaging , Humans , Macular Edema/diagnostic imaging , Retina/diagnostic imaging , Tomography, Optical CoherenceABSTRACT
BACKGROUND: Patients with anti-aquaporin-4 antibody seropositive (AQP4-IgG+) neuromyelitis optica spectrum disorders (NMOSDs) frequently suffer from optic neuritis (ON) leading to severe retinal neuroaxonal damage. Further, the relationship of this retinal damage to a primary astrocytopathy in NMOSD is uncertain. Primary astrocytopathy has been suggested to cause ON-independent retinal damage and contribute to changes particularly in the outer plexiform layer (OPL) and outer nuclear layer (ONL), as reported in some earlier studies. However, these were limited in their sample size and contradictory as to the localisation. This study assesses outer retinal layer changes using optical coherence tomography (OCT) in a multicentre cross-sectional cohort. METHOD: 197 patients who were AQP4-IgG+ and 32 myelin-oligodendrocyte-glycoprotein antibody seropositive (MOG-IgG+) patients were enrolled in this study along with 75 healthy controls. Participants underwent neurological examination and OCT with central postprocessing conducted at a single site. RESULTS: No significant thinning of OPL (25.02±2.03 µm) or ONL (61.63±7.04 µm) were observed in patients who were AQP4-IgG+ compared with patients who were MOG-IgG+ with comparable neuroaxonal damage (OPL: 25.10±2.00 µm; ONL: 64.71±7.87 µm) or healthy controls (OPL: 24.58±1.64 µm; ONL: 63.59±5.78 µm). Eyes of patients who were AQP4-IgG+ (19.84±5.09 µm, p=0.027) and MOG-IgG+ (19.82±4.78 µm, p=0.004) with a history of ON showed parafoveal OPL thinning compared with healthy controls (20.99±5.14 µm); this was not observed elsewhere. CONCLUSION: The results suggest that outer retinal layer loss is not a consistent component of retinal astrocytic damage in AQP4-IgG+ NMOSD. Longitudinal studies are necessary to determine if OPL and ONL are damaged in late disease due to retrograde trans-synaptic axonal degeneration and whether outer retinal dysfunction occurs despite any measurable structural correlates.