-
Ophthalmology. Retina Apr 2024
Topics: Humans; Retinal Neoplasms; Vitreous Body; Eye Neoplasms; Lymphoma
PubMed: 38580415
DOI: 10.1016/j.oret.2024.01.024 -
International Journal of Biological... May 2024The vitreous is a vital component of the eye, occupying a substantial portion of its volume and maintaining its structure. This study delves into the presence and...
The vitreous is a vital component of the eye, occupying a substantial portion of its volume and maintaining its structure. This study delves into the presence and significance of intrinsically disordered proteins (IDPs) within the vitreous, utilizing a dataset of 1240 vitreous proteins previously discovered in the vitreous proteome by Murthy et al.in five healthy subjects. The results indicate that 26.9 % of vitreous proteins are highly disordered, 68.8 % possess moderate disorder, and only 4.3 % are highly ordered. A complex interaction network among these proteins suggests their biological importance, and approximately 25 % may undergo liquid-liquid phase separation (LLPS). These findings offer new perspectives on the vitreous' molecular composition and behavior, potentially impacting our understanding of eye-related diseases, physiological changes such as vitreous syneresis. Further research is needed to translate these insights into clinical applications, although the intrinsic protein disorder and its association with LLPS appears to play a role in vitreous proteome function.
Topics: Humans; Intrinsically Disordered Proteins; Proteome; Vitreous Body; Eye Proteins
PubMed: 38569991
DOI: 10.1016/j.ijbiomac.2024.131274 -
Graefe's Archive For Clinical and... Apr 2024Originally discovered in the nineteenth century, hyalocytes are the resident macrophage cell population in the vitreous body. Despite this, a comprehensive understanding... (Review)
Review
Originally discovered in the nineteenth century, hyalocytes are the resident macrophage cell population in the vitreous body. Despite this, a comprehensive understanding of their precise function and immunological significance has only recently emerged. In this article, we summarize recent in-depth investigations deciphering the critical role of hyalocytes in various aspects of vitreous physiology, such as the molecular biology and functions of hyalocytes during development, adult homeostasis, and disease. Hyalocytes are involved in fetal vitreous development, hyaloid vasculature regression, surveillance and metabolism of the vitreoretinal interface, synthesis and breakdown of vitreous components, and maintenance of vitreous transparency. While sharing certain resemblances with other myeloid cell populations such as retinal microglia, hyalocytes possess a distinct molecular signature and exhibit a gene expression profile tailored to the specific needs of their host tissue. In addition to inflammatory eye diseases such as uveitis, hyalocytes play important roles in conditions characterized by anomalous posterior vitreous detachment (PVD) and vitreoschisis. These can be hypercellular tractional vitreo-retinopathies, such as macular pucker, proliferative vitreo-retinopathy (PVR), and proliferative diabetic vitreo-retinopathy (PDVR), as well as paucicellular disorders such as vitreo-macular traction syndrome and macular holes. Notably, hyalocytes assume a significant role in the early pathophysiology of these disorders by promoting cell migration and proliferation, as well as subsequent membrane contraction, and vitreoretinal traction. Thus, early intervention targeting hyalocytes could potentially mitigate disease progression and prevent the development of proliferative vitreoretinal disorders altogether, by eliminating the involvement of vitreous and hyalocytes.
PubMed: 38568222
DOI: 10.1007/s00417-024-06448-3 -
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 -
The Association of Intraocular Efavirenz Concentrations and HIV-1 Viral Load Among Persons With HIV.Journal of Acquired Immune Deficiency... Jul 2024Efavirenz (EFV) is commonly used in combination antiretroviral therapy. However, in our previous study, many persons living with HIV exhibited ocular complications... (Observational Study)
Observational Study
OBJECTIVE
Efavirenz (EFV) is commonly used in combination antiretroviral therapy. However, in our previous study, many persons living with HIV exhibited ocular complications despite undergoing effective combination antiretroviral therapy. Here, we aimed to determine the intraocular EFV concentrations in the vitreous and analyze the factors affecting viral load in the vitreous in patients with HIV-associated retinopathies.
DESIGN
Observational, retrospective study.
METHODS
Fourteen patients receiving EFV in combination with an antiretroviral therapy who underwent pars plana vitrectomy were enrolled between January 2019 and August 2022. The patients were divided into 2 groups based on presence or absence of retinal detachment (RD). Patient characteristics and HIV-1 RNA levels in plasma and vitreous were recorded during pars plana vitrectomy. Paired blood plasma and vitreous samples were obtained for EFV concentration analysis using ultra-high-performance liquid chromatography/tandem mass spectrometry.
RESULTS
The median age of the enrolled patients was 48 years (interquartile range, 32.25-53.25), including 12 men and 2 women. Median vitreous and plasma EFV concentrations were 141.5 (interquartile range, 69.63-323.75) and 2620 ng/mL (1680-4207.5), respectively. Median ratio of vitreous/plasma EFV concentrations in the paired samples among all participants was 0.053 (0.018-0.118). Median vitreous/plasma EFV concentrations significantly differed between the non-RD and RD groups (0.04 vs 0.12, P = 0.042).
CONCLUSIONS
The vitreous EFV concentrations were insufficient to inhibit viral replication in intraocular tissues, which may be because of poor penetration of the blood-retinal barrier. High vitreous EFV concentrations were associated with RD, indicating a correlation between the EFV concentration and the severity of blood-retinal barrier disruption. It implied that EFV was not a suitable antiviral drug to inhibit HIV-1 replication in ocular tissues.
Topics: Humans; Benzoxazines; Alkynes; Cyclopropanes; Male; Female; HIV Infections; Viral Load; HIV-1; Middle Aged; Adult; Retrospective Studies; Anti-HIV Agents; Vitreous Body; RNA, Viral; Vitrectomy
PubMed: 38534141
DOI: 10.1097/QAI.0000000000003426 -
International Ophthalmology Clinics Apr 2024Proliferative vitreoretinopathy (PVR) is a complication of retinal detachment (RD) that is characterized by the development of retinal stiffness and contractile...
Proliferative vitreoretinopathy (PVR) is a complication of retinal detachment (RD) that is characterized by the development of retinal stiffness and contractile membranes on the surface or underside of the retina. It can occur in primary RD and make repair more challenging, or it can occur following initial successful RD repair and lead to re-detachment. Though our understanding of the pathophysiology underlying PVR membrane formation has grown based on cellular and animal models, there remains no currently approved medical therapy for treatment or prevention of PVR. Though some pharmacologic agents remain under active investigation, many have failed to show consistent benefit in human trials despite promising results from preclinical models. Further research is essential not only to enhance our understanding of PVR pathophysiology but also to identify novel therapeutic strategies for treating PVR in human patients.
Topics: Humans; Vitreoretinopathy, Proliferative; Vitreous Body; Vitrectomy; Retinal Detachment
PubMed: 38525986
DOI: 10.1097/IIO.0000000000000495