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International Journal of Biological... Apr 2024The utilization of neurotrophins in medicine shows significant potential for addressing neurodegenerative conditions, such as age-related macular degeneration (AMD)....
The utilization of neurotrophins in medicine shows significant potential for addressing neurodegenerative conditions, such as age-related macular degeneration (AMD). However, the therapeutic use of neurotrophins has been restricted due to their short half-life. Here, we aimed to synthesize PEGylated nanoparticles based on electrostatic-driven interactions between human serum albumin (HSA), a carrier for adsorption; neurotrophin-3 (NT3); and brain-derived neurotrophic factor (BDNF). Electrophoretic (ELS) and multi-angle dynamic light scattering (MADLS) revealed that the PEGylated HSA-NT3-BDNF nanoparticles ranged from 10 to 430 nm in diameter and exhibited a low polydispersity index (<0.4) and a zeta potential of -8 mV. Based on microscale thermophoresis (MST), the estimated dissociation constant (K) from the HSA molecule of BDNF was 1.6 μM, and the K of NT3 was 732 μM. The nanoparticles were nontoxic toward ARPE-19 and L-929 cells in vitro and efficiently delivered BDNF and NT3. Based on the biodistribution of neurotrophins after intravitreal injection into BALB/c mice, both nanoparticles were gradually released in the mouse vitreous body within 28 days. PEGylated HSA-NT3-BDNF nanoparticles stabilize neurotrophins and maintain this characteristic in vivo. Thus, given the simplicity of the system, the nanoparticles may enhance the treatment of a variety of neurological disorders in the future.
Topics: Mice; Humans; Animals; Brain-Derived Neurotrophic Factor; Tissue Distribution; Membrane Potentials; Polyethylene Glycols
PubMed: 38490392
DOI: 10.1016/j.ijbiomac.2024.130726 -
European Journal of Pharmaceutics and... May 2024Even though subconjunctival injections are used in clinics, their quantitative pharmacokinetics has not been studied systematically. For this purpose, we evaluated the...
Even though subconjunctival injections are used in clinics, their quantitative pharmacokinetics has not been studied systematically. For this purpose, we evaluated the ocular and plasma pharmacokinetics of subconjunctival dexamethasone in rabbits. Intravenous injection was also given to enable a better understanding of the systemic pharmacokinetics. Dexamethasone concentrations in plasma (after subconjunctival and intravenous injections) and four ocular tissues (iris-ciliary body, aqueous humour, neural retina and vitreous) were analysed using LC-MS/MS. Population pharmacokinetic modelling for plasma data from both injection routes were used, and for first time the constant rate of absorption of dexamethasone from the subconjunctival space into plasma was estimated (k = 0.043 min, i.e. absorption half-life of 17.3 min). Non-compartmental analysis was used for the ocular data analysis and resulting in ocular drug exposure of iris-ciliary body (AUC= 41984 min·ng/g) > neural retina (AUC= 25511 min·ng/g) > vitreous (AUC= 7319 min·ng/mL) > aqueous humour (AUC= 6146 min·ng/mL). The absolute bioavailability values after subconjunctival injection, reported for the first time, were 0.74 % in aqueous humour (comparable to topical dexamethasone suspensions), and 0.30 % in vitreous humour (estimated to be higher than in topical administration). These novel and comprehensive pharmacokinetic data provide valuable information on the potential for exploiting this route in ocular drug development for treating both, anterior and posterior segment ocular diseases. Moreover, the new generated dexamethasone-parameters are a step-forward in building predictive pharmacokinetic models to support the design of new subconjunctival dexamethasone formulations, which may sustain drug effect for longer period of time.
Topics: Animals; Rabbits; Injections, Intravenous; Chromatography, Liquid; Tandem Mass Spectrometry; Vitreous Body; Dexamethasone
PubMed: 38484852
DOI: 10.1016/j.ejpb.2024.114260 -
Clinical Ophthalmology (Auckland, N.Z.) 2024We studied the kinetic phenomenon of an airbag impact on eyes with different axial lengths using finite element analysis (FEA) to sequentially determine the physical and...
BACKGROUND
We studied the kinetic phenomenon of an airbag impact on eyes with different axial lengths using finite element analysis (FEA) to sequentially determine the physical and mechanical responses of intraocular segments at various airbag deployment velocities.
METHODS
The human eye model we created was used in simulations with the FEA program PAM-GENERIS. The airbag was set to impact eyes with axial lengths of 21.85 mm (hyperopia), 23.85 mm (emmetropia) and 25.85 mm (myopia), at initial velocities of 20, 30, 40, 50 and 60 m/s. The deformation rate was calculated as the ratio of the length of three segments, anterior chamber, lens and vitreous, to that at the baseline from 0.2 ms to 2.0 ms after the airbag impact.
RESULTS
Deformation rate of the anterior chamber was greater than that of other segments, especially in the early phase, 0.2-0.4 ms after the impact (P < 0.001), and it reached its peak, 80%, at 0.8 ms. A higher deformation rate in the anterior chamber was found in hyperopia compared with other axial length eyes in the first half period, 0.2-0.8 ms, followed by the rate in emmetropia (P < 0.001). The lens deformation rate was low, its peak ranging from 40% to 75%, and exceeded that of the anterior chamber at 1.4 ms and 1.6 ms after the impact (P < 0.01). The vitreous deformation rate was lower throughout the simulation period than that of the other segments and ranged from a negative value (elongation) in the later phase.
CONCLUSION
Airbag impact on the eyeball causes evident deformation, especially in the anterior chamber. The results obtained in this study, such as the time lag of the peak deformation between the anterior chamber and lens, suggest a clue to the pathophysiological mechanism of airbag ocular injury.
PubMed: 38468913
DOI: 10.2147/OPTH.S445253 -
Frontiers in Immunology 2024The aim of this study was to identify inflammatory biomarkers in traumatic proliferative vitreoretinopathy (TPVR) patients and further validate the expression curve of...
BACKGROUND
The aim of this study was to identify inflammatory biomarkers in traumatic proliferative vitreoretinopathy (TPVR) patients and further validate the expression curve of particular biomarkers in the rabbit TPVR model.
METHODS
The Olink Inflammation Panel was used to compare the differentially expressed proteins (DEPs) in the vitreous of TPVR patients 7-14 days after open globe injury (OGI) ( = 19) and macular hole patients ( = 22), followed by correlation analysis between DEPs and clinical signs, protein-protein interaction (PPI) analysis, area under the receiver operating characteristic curve (AUC) analysis, and function enrichment analysis. A TPVR rabbit model was established and expression levels of candidate interleukin family members (IL-6, IL-7, and IL-33) were measured by enzyme-linked immunosorbent assay (ELISA) at 0, 1, 3, 7, 10, 14, and 28 days after OGI.
RESULTS
Forty-eight DEPs were detected between the two groups. Correlation analysis showed that CXCL5, EN-RAGE, IL-7, ADA, CD5, CCL25, CASP8, TWEAK, and IL-33 were significantly correlated with clinical signs including ocular wound characteristics, PVR scoring, PVR recurrence, and final visual acuity ( = 0.467-0.699, < 0.05), and all with optimal AUC values (0.7344-1). Correlations between DEP analysis and PPI analysis further verified that IL-6, IL-7, IL-8, IL-33, HGF, and CXCL5 were highly interactive (combined score: 0.669-0.983). These DEPs were enriched in novel pathways such as cancer signaling pathway ( = 14, < 0.000). Vitreous levels of IL-6, IL-7, and IL-33 in the rabbit TPVR model displayed consistency with the trend in Olink data, all exhibiting marked differential expression 1 day following the OGI.
CONCLUSION
IL-7, IL-33, EN-RAGE, TWEAK, CXCL5, and CD5 may be potential biomarkers for TPVR pathogenesis and prognosis, and early post-injury may be an ideal time for TPVR intervention targeting interleukin family biomarkers.
Topics: Humans; Rabbits; Animals; Vitreoretinopathy, Proliferative; Vitreous Body; Interleukin-33; Interleukin-6; Interleukin-7; Proteomics; Prognosis; Biomarkers
PubMed: 38455059
DOI: 10.3389/fimmu.2024.1355314 -
BMC Ophthalmology Mar 2024To report a case of unusual presentation of retinochoroiditis caused by Rickettsia typhi in a patient without prior uveitis.
BACKGROUND
To report a case of unusual presentation of retinochoroiditis caused by Rickettsia typhi in a patient without prior uveitis.
CASE PRESENTATION
In this case, we describe a 24-year-old male soldier with no previous eye disease, who was referred to our ophthalmology department due to bilateral retinochoroiditis and vitritis. The patient initially presented with a paracentral scotoma in his right eye persisting for 7 days and scattered dark spots in his left eye for 2 days in June 2023. Preceding these ocular symptoms, he experienced a two-week episode of fever, headaches, night sweats, and rapid weight loss of 10 kg. A transient rash covered his body briefly. His mother had a history of recurrent eye inflammation. Physical examination revealed bilateral keratic precipitates on the lower corneal periphery, 1 + anterior vitreous cells, small retinal lesions and mild optic discs elevation. Fluorescein angiography indicated mild discs hyperfluorescence, and the clinically visible round punctate lesions on OCT showed inner retinal hyper-reflective lesion with a depth till outer plexiform layer possibly suggestive of a retinitis lesion. Laboratory tests were normal except thrombocytosis, elevated ESR, liver enzymes and ACE levels, with positive Rickettsia typhi serology tests. Rheumatology and infectious disease consultations ruled out autoimmune diseases, confirming Rickettsia typhi infection. Treatment included systemic doxycycline and prednisone, with improvement of visual acuity, ocular symptoms, OCT abnormalities and resolution of inflammation. Prednisone was discontinued, and after two months, additional improvement was seen clinically, with preserved retinal structures on OCT.
CONCLUSION
This study explores retinochoroiditis as a rare ocular presentation of Rickettsia typhi, an unusual infection in the Middle East. Previously reported ocular manifestations include conjunctivitis, vitritis, post infectious optic neuropathy and a few cases of uveitis. Ocular symptoms followed systemic illness, highlighting the need for awareness among clinicians. Diagnosis relies on seroconversion, with fluorescein angiography and OCT aiding in assessment. Empiric doxycycline and systemic corticosteroid therapy is recommended. Ocular symptoms resolved in two months. Awareness of these ocular manifestations is essential for timely diagnosis and management. Further research is needed to fully understand this aspect of murine typhus.
Topics: Humans; Male; Young Adult; Chorioretinitis; Doxycycline; Inflammation; Prednisone; Typhus, Endemic Flea-Borne
PubMed: 38454387
DOI: 10.1186/s12886-024-03329-5 -
Asia-Pacific Journal of Ophthalmology... 2024
Topics: Humans; Male; Eye Neoplasms; Melanoma; Neoplasm Recurrence, Local; Neoplasm Seeding; Uveal Neoplasms; Vitreous Body
PubMed: 38453030
DOI: 10.1016/j.apjo.2024.100048 -
BMC Ophthalmology Mar 2024To evaluate the association of body stature with ocular biometrics and refraction in preschool children.
PURPOSE
To evaluate the association of body stature with ocular biometrics and refraction in preschool children.
METHODS
A cross-sectional, school-based study was conducted in Shenzhen, China. Preschool children aged 3 to 6 from 10 randomly-selected kindergartens were recruited. Ocular biometric parameters, including axial length (AL), anterior chamber depth (ACD), vitreous chamber depth (VCD), corneal radius curvature (CR), axial length to corneal radius ratio (AL-to-CR ratio) and lens thickness (LT) were measured using non-contact partial-coherence laser interferometry. Cycloplegic refractions were obtained by a desktop autorefractor. Body height and weight were measured using standard procedures. The association between body stature and ocular biometrics were analyzed with univariable and multivariable regression model.
RESULTS
A total of 373 preschoolers were included. AL, ACD, VCD, CR, and AL-to-CR ratio, were positively associated with height and weight (p < 0.05), whereas LT was negatively associated with height and weight (p < 0.01). No association was observed between stature and central cornea thickness and refraction. After adjusted for age and gender in a multivariable regression model, AL had positive associations with height (p < 0.01) and weight (p < 0.01). However, refraction had no significant association with stature parameters.
CONCLUSION
Taller and heavier preschoolers had eyes with longer AL, deeper vitreous chamber, and flatter cornea. The significant associations between body stature and ocular biometric parameters reveal the driving influence of body development on the growth of eyeballs in preschoolers.
Topics: Child, Preschool; Humans; Body Height; Cross-Sectional Studies; Anterior Eye Segment; Biometry; China
PubMed: 38448947
DOI: 10.1186/s12886-024-03372-2 -
International Journal of Retina and... Mar 2024To assess the characteristics and outcomes of uveal melanoma management at a tertiary center in the Middle East.
BACKGROUND
To assess the characteristics and outcomes of uveal melanoma management at a tertiary center in the Middle East.
METHODS
A study on 164 patients with uveal melanoma was conducted by reviewing the available medical records, ultrasound, and pathology report results. Age at diagnosis, tumor location and size, treatment mode, visual outcome, metastasis, mortality, and survival were studied.
RESULTS
The mean age of patients was 52.0 ± 15.0 years, and 52.5% were male. Choroidal melanoma was the most common uveal melanoma, followed by the ciliary body and iris melanoma. The mean thickness of tumors was 8.29 ± 3.29. The majority of patients (n = 111, 67.9%) were managed by brachytherapy with ruthenium-106 plaques. Enucleation was performed primarily in 46 (28%) patients and secondarily in nine (5.5%) patients. The sexual disparity was detected as the proximity of uveal melanoma to the fovea in males. For a 61-month mean follow-up period, mortality occurred in eight of our cases, six of which were due to metastasis. The most common site for distance metastasis was the liver (5/6), followed by the lung (1/6). The five-year and eight-year overall survival (OS) rate was 0.947%± 0.019. The 5-year survival rate reached zero in metastatic patients. OS was not statistically different depending on the age, tumor diameters, the primary treatment received, or the histopathologic findings (p > 0.50 for all).
CONCLUSION
In this study, individuals diagnosed with UM exhibited an OS rate of around 94% at the five-year mark, which remained consistent up to eight years. Notably, the presence of distance metastasis emerged as the sole statistically significant factor influencing overall survival.
PubMed: 38429783
DOI: 10.1186/s40942-024-00531-x