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Journal of Controlled Release :... Jun 2024Lipid-based drug formulations are promising systems for improving delivery of drugs to ocular tissues, such as retina. To develop lipid-based systems further, an...
Lipid-based drug formulations are promising systems for improving delivery of drugs to ocular tissues, such as retina. To develop lipid-based systems further, an improved understanding of their pharmacokinetics is required, but high-quality in vivo experiments require a large number of animals, raising ethical and economic questions. In order to expedite in vivo kinetic testing of lipid-based systems, we propose a barcode approach that is based on barcoding liposomes with non-endogenous lipids. We developed and evaluated a liquid-chromatography-mass spectrometry method to quantify many liposomes simultaneously in aqueous humor, vitreous, and neural retina at higher than ±20% precision and accuracy. Furthermore, we showed in vivo suitability of the method in pharmacokinetic evaluation of six different liposomes after their simultaneous injection into the rat vitreal cavity. We calculated pharmacokinetic parameters in vitreous and aqueous humor, quantified liposome concentrations in the retina, and quantitated retinal distribution of the liposomes in the rats. Compared to individual injections of the liposome formulations, the barcode-based study design enabled reduction of animal numbers from 72 to 12. We believe that the proposed approach is reliable and will reduce and refine ocular pharmacokinetic experiments with liposomes and other lipid-based systems.
Topics: Animals; Liposomes; Vitreous Body; Aqueous Humor; Lipids; Retina; Male; Rats; Eye; Mass Spectrometry; Chromatography, Liquid; Rats, Sprague-Dawley; Tissue Distribution
PubMed: 38615893
DOI: 10.1016/j.jconrel.2024.04.023 -
BMC Ophthalmology Apr 2024To describe a case of bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus (WNV) infection in the absence of neurological involvement.
BACKGROUND
To describe a case of bilateral multifocal chorioretinitis as the only presentation of acute West Nile virus (WNV) infection in the absence of neurological involvement.
CASE PRESENTATION
A 78-year-old Italian woman was admitted to our emergency department because she noticed blurry vision in both eyes. She did not report fever, fatigue, or neurological symptoms in the last few days. Multimodal imaging showed the presence of bilateral hyperfluorescent lesions with a linear distribution, that corresponded to hypocyanescent spots on indocyanine green angiography. Antibody serology showed the presence of IgM antibodies, IgG antibodies, and ribonucleic acid (RNA) for WNV. Magnetic resonance imaging (MRI) of the brain ruled out central nervous system involvement. Three months later, the patient reported spontaneous resolution of her symptoms and remission of the chorioretinal infiltrates.
CONCLUSIONS
In endemic areas, it is important to think of acute WNV infection as an explanatory etiology in cases of multifocal chorioretinitis, even without neurological involvement.
Topics: Humans; Female; Aged; West Nile Fever; West Nile virus; Eye Infections, Viral; Chorioretinitis; Vitreous Body; Antibodies, Viral
PubMed: 38600458
DOI: 10.1186/s12886-024-03423-8 -
Asia-Pacific Journal of Ophthalmology... 2024
Topics: Humans; Carcinoma, Renal Cell; Endophthalmitis; Kidney Neoplasms; Vitreous Body; Diagnosis, Differential; Male; Eye Neoplasms; Middle Aged; Cytology
PubMed: 38583527
DOI: 10.1016/j.apjo.2024.100055 -
ABCA4 mediated traumatic proliferative vitreoretinopathy associated with PI3K/Akt signaling pathway.Heliyon Apr 2024Proliferative vitreoretinopathy (PVR) is the main cause of retinal detachment. However, the underlying mechanism of PVR is complex and has not yet been fully elucidated....
BACKGROUND
Proliferative vitreoretinopathy (PVR) is the main cause of retinal detachment. However, the underlying mechanism of PVR is complex and has not yet been fully elucidated. The PI3K/Akt/mTOR signaling pathway is involved in angiogenesis and plays an important role in cell proliferation and tumor formation. Therefore, our study was designed to investigate the potential biological mechanisms of alleviating ARPE-19 cell and traumatic PVR model involving PI3K/Akt signaling pathway by targeting ABCA4.
MATERIALS AND METHODS
ARPE-19 cell model was induced by ABCA4 overexpression vector and si-ABCA4, then the ABCA4 overexpression vector and si-ABCA4 were constructed, the plasmids were expanded for cell transfection and verification. In addition, OE-ABCA4, shRNA NC and si-ABCA4 were transfected into ARPE-19 cells. Cell viability was detected by CCK-8 assay, cell cycle was determined by flow cytometry. The expression level and location of ABCA4 were detected by immunofluorescence. Finally, rabbit traumatic PVR model was induced by surgery, the adenovirus was injected into the vitreous body respectively, and the fundus observation was performed by direct ophthalmoscope observation combined with fundus photography, and the retinal routine histopathology HE staining was performed. Analysis of P21, CDK4, Cyclin D1, BAX, BAD, and ABCA4 was used by quantitative RT-PCR and Western blot. Besides, the expression level of ABCA4, AKT, -AKT, PI3K, p-PI3K, P38, p-P38, JNK, -JNK, ERK, and -ERK was detected by Western blot.
RESULTS
All results indicated that the viability of cells with high expression of ABC4A increased, while the viability of cells with inhibition of ABC4A decreased, the number of cells with high ABC4A expression was significantly higher, and the migration level of cells was significantly reduced after ABC4A inhibition (P < 0.05). ABC4A could affect cell apoptosis by affecting G1/G2 phase. The cell proliferation level was significantly increased with high expression of ABC4A. High expression of ABC4A increased phosphorylation levels, including -AKT, -PIK3, and p-P38, while inhibition of ABC4A decreased the expression levels of these proteins (P < 0.05). Inhibition of ABC4A could significantly improve retinopathy, indicating that the proliferation ability of cells was restored after inhibition of ABC4A.
CONCLUSIONS
Our finding suggested that inhibition of ABC4A ameliorated the injury degree of traumatic PVR and performed the potential anti-PVR effect via inhibiting PI3K/Akt signaling pathway, while promoting cell proliferation in both rabbit and ARPE-19 cells PVR model. The study has a certain innovation by building a traumatic PVR model to explore whether the ABCA4 participates in the regulation of the PI3K/AKT signaling pathway and the pathological mechanism of PVR regulation. At the same time, ABCA4's participation in the regulation of PI3K/Akt signaling pathway can prevent and delay the occurrence and development of PVR, which has positive significance for improving the survival rate and quality of life of patients, and also provides an important basis for its therapeutic mechanism. Therefore, our study demonstrated a significant strategy for inhibiting traumatic PVR via targeting PI3K/Akt/ABCA4 pathway.
PubMed: 38560110
DOI: 10.1016/j.heliyon.2024.e27024 -
American Journal of Ophthalmology Case... Jun 2024To report a case of secondary Multiple Evanescent White Dot Syndrome in a patient with preexisting wet age-related macular degeneration.
PURPOSE
To report a case of secondary Multiple Evanescent White Dot Syndrome in a patient with preexisting wet age-related macular degeneration.
OBSERVATION
A 75-year-old male on treat and extend regimen for wet age-related macular degeneration (AMD) presented with a sudden loss of vision and saw central dark shadow in the right eye (RE) for a duration of 1 week. There was no significant history preceding the visual loss. Examination showed a visual acuity (VA) of counting fingers at 1 meter in the right eye and 20/25 in the left eye. Anterior segment examination was unremarkable with dilated fundus examination showing a clear vitreous, tortuous blood vessel, a hyperemic disc and fibrosis at the macula. The left eye (LE) examination was unremarkable. Optical Coherence Tomography (OCT) showed fibrosis due to the previous wet AMD and hyperreflective excrescences projecting from the retinal pigment epithelium (RPE) outside of the old area of wet AMD. Fundus Fluorescein Angiogram (FFA) showed hyperfluorescent spots in a wreath-like pattern increasing in intensity in the early phase and showing late staining towards the late phase while Indocyanine green angiography (ICGA) did not clearly delineate the lesions. Fundus autofluorescence (FAF) revealed hyper Autofluorescence (AF) at the posterior pole. Optical Coherence Tomography Angiography (OCTA) revealed a flow reduction in the choriocapillaris of the affected area. Basic blood investigations with Venereal Disease Research Laboratory (VDRL), syphilitic IgM and IgG antibodies, Quantiferon TB gold test, complete renal function tests and liver function tests were performed. All the blood investigations were within normal limits and the workup for syphilis and tuberculosis was negative. The patient was started on 1mg/kg body weight of oral prednisolone (after the non-response to low dose of oral steroids) with the diagnosis of secondary multiple evanescent white dot syndrome (MEWDS) secondary to wet AMD. The patient was followed up every weekly and the last visit showed improvement in visual acuity to 20/50 with resolution of lesions on FAF and OCT macula.
CONCLUSION AND IMPORTANCE
Secondary MEWDS is extremely rare and unique in terms of its presentation and its association with preexisting chorioretinal disease where there is damage to the choriocapillaris- Bruch's membrane-RPE complex. This case report highlights one such rare case scenario and how multimodal imaging helps in the diagnosis, management and follow-up of patients with secondary MEWDS.
PubMed: 38559365
DOI: 10.1016/j.ajoc.2024.102016 -
Investigative Ophthalmology & Visual... Mar 2024Symptomatic vitreous opacifications, so-called floaters, are difficult to objectively assess majorly limiting the possibility of in vitro studies. Forward light...
PURPOSE
Symptomatic vitreous opacifications, so-called floaters, are difficult to objectively assess majorly limiting the possibility of in vitro studies. Forward light scattering was found previously to be increased in eyes with symptomatic floaters. Using an objective setup to measure forward light scattering, we studied the effects of enzymatically digesting the components of the vitreous body on straylight to develop an in vitro model of vitreous opacifications.
METHODS
Fifty-seven porcine vitreous bodies were digested using hyaluronidase, collagenase, trypsin, and bromelain, as well as using a combination of hyaluronidase + collagenase and hyaluronidase + bromelain. A modified C-Quant setup was used to objectively assess forward light scattering.
RESULTS
Depletion of hyaluronic acid majorly increased vitreous straylight (mean increase 34.4 deg2/sr; P = 0.01), whereas primarily digesting the vitreous gel with collagenase or trypsin did not significantly affect straylight. When collagenase or bromelain is applied in hyaluronic acid depleted vitreous gels, the increase in forward light scattering is reversed partially.
CONCLUSIONS
The age-related loss of hyaluronic acid primarily drives the increase in vitreous gel straylight induced by conglomerates of collagen. This process can be reversed partially by digesting collagen. This in vitro model allows the objective quantification and statistical comparison of straylight burden caused by vitreous opacities and, thus, can serve as a first testing ground for pharmacological therapies, as demonstrated with bromelain.
Topics: Animals; Swine; Light; Bromelains; Hyaluronoglucosaminidase; Hyaluronic Acid; Trypsin; Aging; Collagen; Collagenases; Scattering, Radiation
PubMed: 38551585
DOI: 10.1167/iovs.65.3.36 -
Biomedicines Mar 2024Glaucoma is a multifactorial pathology involving the immune system. The subclinical immune response plays a homeostatic role in healthy situations, but in pathological...
Glaucoma is a multifactorial pathology involving the immune system. The subclinical immune response plays a homeostatic role in healthy situations, but in pathological situations, it produces imbalances. Optical coherence tomography detects immune cells in the vitreous as hyperreflective opacities and these are subsequently characterised by computational analysis. This study monitors the changes in immunity in the vitreous in two steroid-induced glaucoma (SIG) animal models created with drug delivery systems (microspheres loaded with dexamethasone and dexamethasone/fibronectin), comparing both sexes and healthy controls over six months. SIG eyes tended to present greater intensity and a higher number of vitreous opacities ( < 0.05), with dynamic fluctuations in the percentage of isolated cells (10 µm), non-activated cells (10-50 µm), activated cells (50-250 µm) and cell complexes (>250 µm). Both SIG models presented an anti-inflammatory profile, with non-activated cells being the largest population in this study. However, smaller opacities (isolated cells) seemed to be the first responder to noxa since they were the most rounded (recruitment), coinciding with peak intraocular pressure increase, and showed the highest mean Intensity (intracellular machinery), even in the contralateral eye, and a major change in orientation (motility). Studying the features of hyperreflective opacities in the vitreous using OCT could be a useful biomarker of glaucoma.
PubMed: 38540246
DOI: 10.3390/biomedicines12030633 -
Ceska a Slovenska Oftalmologie :... 2024Retinoblastoma is the most common primary malignant intraocular tumor in children. Seeding, specifically the dispersion of the tumor into the adjacent compartments,... (Review)
Review
Retinoblastoma is the most common primary malignant intraocular tumor in children. Seeding, specifically the dispersion of the tumor into the adjacent compartments, represents a major parameter determining the degree of retinoblastoma according to the International Classification of Retinoblastoma. In this article we focused on vitreous seeding, one of the main limiting factors in the successful "eye preservation treatment" of retinoblastoma. This article presents an overview of the history of vitreous seeding of retinoblastoma, established treatment procedures and new-research modalities. The introduction of systemic chemotherapy in the treatment of retinoblastoma at the end of the 1990s represented a significant breakthrough, which enabled the progressive abandonment of radiotherapy with its attendant side effects. However, the attained concentrations of chemotherapeutics in the vitreous space during systemic chemotherapy are not sufficient for the treatment of vitreous seeding, and the toxic effects of systemic chemotherapy are not negligible. A significant change came with the advent of chemotherapy in situ, with the targeted administration of chemotherapeutic drugs, namely intra-arterial and intravitreal injections, contributing to the definitive eradication of external radiotherapy and a reduction of systemic chemotherapy. Although vitreous seeding remains the most common reason for the failure of intra-arterial chemotherapy, this technique has significantly influenced the original treatment regimen of children with retinoblastoma. However, intravitreal chemotherapy has made the greatest contribution to increasing the probability of preservation of the eyeball and visual functions in patients with advanced findings. Novel local drug delivery modalities, gene therapy, oncolytic viruses and immunotherapy from several ongoing preclinical and clinical trials may represent promising approaches in the treatment of vitreous retinoblastoma seeding, though no clinical trials have yet been completed for routine use.
Topics: Child; Humans; Retinoblastoma; Retinal Neoplasms; Melphalan; Antineoplastic Agents, Alkylating; Vitreous Body; Intravitreal Injections; Retrospective Studies
PubMed: 38538290
DOI: 10.31348/2023/35 -
Scientific Reports Mar 2024The aim of this study was to investigate the anatomical and physiological ocular parameters in adolescents with myopia and to examine the relations between refractive...
The aim of this study was to investigate the anatomical and physiological ocular parameters in adolescents with myopia and to examine the relations between refractive error (SER), ocular biometry, body size and flexibility parameters in myopic adolescents. A cross-sectional study of 184 myopic adolescents, aged 15 to 19 years was conducted. Refractive error and corneal curvature measures of the eye were evaluated using an autorefractometer under cycloplegia. Central corneal thickness was determined by contact pachymetry. The ocular axial length, anterior and vitreous chamber depth, and lens thickness were measured using A-scan biometry ultrasonography. Height and body weight were measured according to a standardized protocol. Body mass index (BMI) was subsequently calculated. Beighton scale was used to measure joint flexibility. Body stature was positively correlated with ocular axial length (r = 0.39, p < 0.001) and vitreous chamber depth (r = 0.37, p < 0.001). There was a negative correlation between height and SER (r = - 0.46; p < 0.001). Beighton score and body weight had weak positive correlations with axial length and vitreous chamber depth, and a weak negative correlation with SER. A significantly more negative SER was observed in the increased joint mobility group (p < 0.05; U = 5065.5) as compared to normal joint mobility group: mean - 4.37 ± 1.85 D (median - 4.25; IQR - 6.25 to - 3.25 D) and mean - 3.72 ± 1.66 D (median - 3.50; IQR - 4.75 to - 2.25 D) respectively. There was a strong association between height and axial length, as well as SER. Higher degree of myopia significantly correlated with greater Beighton score (increased joint mobility).
Topics: Adolescent; Humans; Cross-Sectional Studies; Eye; Myopia; Refractive Errors; Biometry; Body Weight; Anterior Eye Segment; Refraction, Ocular; Anterior Chamber; Axial Length, Eye
PubMed: 38514709
DOI: 10.1038/s41598-024-57347-w -
Asia-Pacific Journal of Ophthalmology... 2024
Topics: Humans; Eye Neoplasms; Immune Checkpoint Inhibitors; Melanoma; Melanoma, Cutaneous Malignant; Skin Neoplasms; Vitreous Body; Female; Middle Aged
PubMed: 38492668
DOI: 10.1016/j.apjo.2024.100050