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Investigative Ophthalmology & Visual... Dec 2014Collagen fiber remodeling in the vitreous body has been implicated in cases of vitreomacular traction, macular hole, and retinal detachment, and also may occur during...
PURPOSE
Collagen fiber remodeling in the vitreous body has been implicated in cases of vitreomacular traction, macular hole, and retinal detachment, and also may occur during pharmacologic vitreolysis. The purpose of this study was to evaluate quantitative polarized light imaging (QPLI) as a tool for studying fiber organization in the vitreous and near the vitreoretinal interface in control and enzymatically perturbed conditions.
METHODS
Fiber alignment was measured in anterior-posterior sections of bovine and porcine vitreous. Additional tests were performed on bovine lenses and nasal-temporal vitreous sections. Effects of proteoglycan degradation on collagen fiber alignment using trypsin and plasmin were assessed at the microstructural level using electron microscopy and at the global level using QPLI.
RESULTS
Control vitreous showed fiber organization patterns consistent with the literature across multiple-length scales, including the global anterior-posterior coursing of vitreous fibers, as well as local fibers parallel to the equatorial vitreoretinal interface and transverse to the posterior interface. Proteoglycan digestion with trypsin or plasmin significantly increased fiber alignment throughout the vitreous (P < 0.01). The largest changes (3×) occurred in the posterior vitreous where fibers are aligned transverse to the posterior vitreoretinal interface (P < 0.01).
CONCLUSIONS
Proteoglycan loss due to enzymatic vitreolysis differentially increases fiber alignment at locations where tractions are most common. We hypothesize that a similar mechanism leads to retinal complications during age-related vitreous degeneration. Structural changes to the entire vitreous body (as opposed to the vitreoretinal interface alone) should be evaluated during preclinical testing of pharmacological vitreolysis candidates.
Topics: Analysis of Variance; Animals; Cattle; Disease Models, Animal; Fibrillar Collagens; Fibrinolysin; Fibrinolytic Agents; Humans; Microscopy, Electron; Microscopy, Polarization; Proteoglycans; Retinal Diseases; Swine; Trypsin; Ultrasonography; Vitreous Body
PubMed: 25468895
DOI: 10.1167/iovs.14-15225 -
System-wide vitreous proteome dissection reveals impaired sheddase activity in diabetic retinopathy.Theranostics 2022Diabetic retinopathy (DR) is a major complication of diabetes mellitus causing significant vision loss. DR is a multifactorial disease involving changes in retinal...
Diabetic retinopathy (DR) is a major complication of diabetes mellitus causing significant vision loss. DR is a multifactorial disease involving changes in retinal microvasculature and neuronal layers, and aberrations in vascular endothelial growth factors (VEGF) and inflammatory pathways. Despite the success of anti-VEGF therapy, many DR patients do not respond well to the treatment, emphasizing the involvement of other molecular players in neuronal and vascular aberrations in DR. We employed advanced mass spectrometry-based proteome profiling to obtain a global snapshot of altered protein abundances in vitreous humor from patients with proliferative DR (PDR) in comparison to individuals with epiretinal membrane without active DR or other retinal vascular complications. Global proteome correlation map and protein-protein interaction networks were used to probe into the functional inclination of proteins and aberrated molecular networks in PDR vitreous. In addition, peptide-centric analysis of the proteome data was carried out to identify proteolytic processing, primarily ectodomain shedding events in PDR vitreous. Functional validation experiments were performed using preclinical models of ocular angiogenesis. The vitreous proteome landscape revealed distinct dysregulations in several metabolic, signaling, and immune networks in PDR. Systematic analysis of altered proteins uncovered specific impairment in ectodomain shedding of several transmembrane proteins playing critical roles in neurodegeneration and angiogenesis, pointing to defects in their regulating sheddases, particularly ADAM10, which emerged as the predominant sheddase. We confirmed that ADAM10 protease activity was reduced in animal models of ocular angiogenesis and established that activation of ADAM10 can suppress endothelial cell activation and angiogenesis. Furthermore, we identified the impaired ADAM10-AXL axis as a driver of retinal angiogenesis. We demonstrate restoration of aberrant ectodomain shedding as an effective strategy for treating PDR and propose ADAM10 as an attractive therapeutic target. In all, our study uncovered impaired ectodomain shedding as a prominent feature of PDR, opening new possibilities for advancement in the DR therapeutic space.
Topics: Animals; Diabetes Mellitus; Diabetic Retinopathy; Peptide Hydrolases; Proteome; Vascular Endothelial Growth Factors; Vitreous Body
PubMed: 36185601
DOI: 10.7150/thno.72947 -
Archiwum Medycyny Sadowej I Kryminologii 2017Biological materials used in toxicological analyses in forensic medicine traditionally include blood, urine and vitreous humour. Forensic use of the vitreous body is...
Biological materials used in toxicological analyses in forensic medicine traditionally include blood, urine and vitreous humour. Forensic use of the vitreous body is mostly due to the need to assess the endogenous concentration of ethyl alcohol in the process of human body decomposition. The vitreous body is an underestimated biological material, even though its biochemical properties and anatomical location make it suitable for specific forensic toxicology tests as a reliable material for the preparation of forensic expert opinions. Based on the available literature the paper gathers information on the biochemical structure of the vitreous body, ways to secure the material after collection and its use in postmortem diagnostics. Specific applications of the vitreous humour for biochemical and toxicological tests are discussed, with a focus on its advantages and limitations in forensic medical assessment which are attributable to its biochemical properties, anatomical location and limited scientific studies on the distribution of xenobiotics in the vitreous body.
Topics: Autopsy; Forensic Medicine; Forensic Toxicology; Humans; Postmortem Changes; Spectrometry, Mass, Electrospray Ionization; Vitreous Body
PubMed: 29460610
DOI: 10.5114/amsik.2017.73192 -
Journal of Ocular Pharmacology and... 2018Even though the very thought of an injection into the eye may be frightening, an estimated 6 million intravitreal (IVT) injections were made in the USA during 2016. With... (Review)
Review
Even though the very thought of an injection into the eye may be frightening, an estimated 6 million intravitreal (IVT) injections were made in the USA during 2016. With the introduction of new therapeutic agents, this number is expected to increase. In addition, drug products that are injectable in ocular compartments other than the vitreous humor are expected to enter the back of the eye market in the not so distant future. Besides the IVT route, some of the most actively investigated routes of invasive administration to the eye include periocular, subretinal, and suprachoroidal (SC) routes. While clinical efficacy is the driving force behind new injectable drug product development for the eye, safety is also being improved with time. In the case of IVT injections, the procedural guidelines have evolved over the years to improve patient comfort and reduce injection-related injury and infection. Similar advances are anticipated for other routes of administration of injectable products to the eye. In addition to procedural improvements, the design of needles, particularly those with smaller diameters, length, and controlled bevel angles are expected to improve overall safety and acceptance of injected ophthalmic drug products. A key development in this area is the introduction of microneedles of a length less than a millimeter that can target the SC space. In the future, needles with smaller diameters and lengths, potentially approaching nanodimensions, are expected to revolutionize ophthalmic disease management.
Topics: Administration, Ophthalmic; Animals; Drug Delivery Systems; Humans; Injections, Intraocular; Intravitreal Injections; Needles; Ophthalmic Solutions; Vitreous Body
PubMed: 29206556
DOI: 10.1089/jop.2017.0121 -
Journal of Clinical Laboratory Analysis Sep 2017Nesfatin-1, belonging to adipokine family, serves as an anti-inflammatory mediator. We performed this investigation to evaluate the relation between serum and vitreous...
OBJECTIVE
Nesfatin-1, belonging to adipokine family, serves as an anti-inflammatory mediator. We performed this investigation to evaluate the relation between serum and vitreous nesfatin-1 concentrations with diabetic retinopathy (DR).
METHODS
This study was performed in a population of 189 diabetic patients and 48 control subjects. Diabetic patients were then divided into diabetic patients without DR, non-proliferative diabetic retinopathy (NPDR) patients, and proliferative diabetic retinopathy (PDR) patients.
RESULTS
Serum and vitreous nesfatin-1 concentrations were significantly lower in the diabetic patients than in the controls. NPDR patients had reduced vitreous nesfatin-1 concentrations compared with patients without DR. In addition, there were significantly lower serum and vitreous nesfatin-1 concentrations in PDR patients compared with the other three groups. Pearson correlation analysis showed that serum nesfatin-1 was negatively correlated with body mass index and fasting plasma glucose in diabetic patients.
CONCLUSION
Serum and vitreous nesfatin-1 concentrations were negatively correlated with DR.
Topics: Aged; Calcium-Binding Proteins; Case-Control Studies; DNA-Binding Proteins; Diabetic Retinopathy; Female; Humans; Male; Middle Aged; Nerve Tissue Proteins; Nucleobindins; Vitreous Body
PubMed: 28079928
DOI: 10.1002/jcla.22105 -
Scientific Reports Oct 2023We conducted a study to assess the pressure difference between the aqueous and vitreous humors in rabbit eyes using a direct intraocular pressure (IOP) measurement...
We conducted a study to assess the pressure difference between the aqueous and vitreous humors in rabbit eyes using a direct intraocular pressure (IOP) measurement method. A micro-optic-fiber pressure sensor was utilized for this purpose. Preliminary experiments with enucleated porcine eyes confirmed the sensor's accuracy in measuring both aqueous and vitreous humor pressure. The main study involved six healthy albino rabbits, where the sensor measured the pressure in the anterior chamber (aIOP) and posterior vitreous-cavity (pIOP). These measurements were compared to aIOP values obtained through rebound tonometry. Additionally, pre- and postoperative pressure comparisons were made after performing a vitrectomy. Results revealed a significant disparity between aqueous and vitreous humor pressures. Prior to vitrectomy, pIOP was 22.8 mmHg, over twice as high as aIOP (11.0 mmHg), but decreased to a similar level following the procedure. Comparison between the sensor measurements and rebound tonometry showed agreement in aIOP values. In conclusion, our study demonstrates that vitreous humor pressure is consistently higher than aqueous humor pressure, reaching the upper limit of normal IOP. Furthermore, vitrectomy effectively reduces pIOP, aligning it with aIOP. These findings contribute valuable insights into intraocular pressure dynamics and have implications for clinical interventions targeting ocular pressure regulation.
Topics: Animals; Swine; Rabbits; Vitreous Body; Intraocular Pressure; Vitrectomy; Tonometry, Ocular; Aqueous Humor
PubMed: 37880357
DOI: 10.1038/s41598-023-45616-z -
Indian Journal of Ophthalmology Sep 2020Pars plana vitrectomy (PPV) in uveitis is indicated for various diagnostic and therapeutic indications. With the advent of microincision vitreous surgery (MIVS), the use... (Review)
Review
Pars plana vitrectomy (PPV) in uveitis is indicated for various diagnostic and therapeutic indications. With the advent of microincision vitreous surgery (MIVS), the use of PPV in uveitis has increased with a wider spectrum of indications due to shorter surgical time, less patient discomfort, less conjunctival scarring, and a decreased rate of complications as compared to standard 20G vitrectomy. Because of faster post-operative recovery in terms of visual improvement and reduction of inflammation, and reduced duration of systemic corticosteroids, MIVS has gained popularity in uveitis as an adjunctive therapy to the standard of care medical therapy. The safety and efficacy of MIVS is related to the emerging vitrectomy techniques with better and newer cutters, illuminating probes, and accessory instruments. Because of the instrumentation and fluidics of MIVS, PPV is emerging as a safe and useful alternative for diagnostic challenges in uveitis, aiding in earlier diagnosis and better outcome of inflammatory disease, even in the presence of severe and active inflammation, which was once considered a relative contraindication for performing vitreous surgery. However, for surgical interventions for therapeutic indications and complications of uveitis, it is advisable to achieve an optimum control of inflammation for best results. The increasing reports of the use of MIVS in uveitis have led to its wider acceptance among clinicians practicing uveitis.
Topics: Humans; Retrospective Studies; Uveitis; Visual Acuity; Vitrectomy; Vitreous Body
PubMed: 32823401
DOI: 10.4103/ijo.IJO_1625_20 -
Retina (Philadelphia, Pa.) May 2023
Topics: Humans; Vitreous Body; Fovea Centralis; Tomography, Optical Coherence; Vitreous Detachment
PubMed: 37068222
DOI: 10.1097/IAE.0000000000003768 -
Antimicrobial Agents and Chemotherapy Dec 2014Caspofungin exhibits potent antifungal activities against Candida and Aspergillus species. The elimination rate and retinal toxicity of caspofungin were determined in...
Caspofungin exhibits potent antifungal activities against Candida and Aspergillus species. The elimination rate and retinal toxicity of caspofungin were determined in this study to assess its pharmacokinetics and safety in the treatment of fungal endophthalmitis. Intravitreal injections of 50 μg/0.1 ml of caspofungin were administered to rabbits. Levels of caspofungin in the vitreous and aqueous humors were determined using high-performance liquid chromatography (HPLC) at selected time intervals (10 min and 1, 2, 4, 8, 16, 24, and 48 h), and the half-lives were calculated. Eyes were intravitreally injected with caspofungin to obtain concentrations of 10 μg/ml, 50 μg/ml, 100 μg/ml, and 200 μg/ml. Electroretinograms were recorded 4 weeks after injections, and the injected eyes were examined histologically. The concentrations of intravitreal caspofungin at various time points exhibited an exponential decay with a half-life of 6.28 h. The mean vitreous concentration was 6.06 ± 1.76 μg/ml 1 h after intravitreal injection, and this declined to 0.47 ± 0.15 μg/ml at 24 h. The mean aqueous concentration showed undetectable levels at all time points. There were no statistical differences in scotopic a-wave and b-wave responses between control eyes and caspofungin-injected eyes. No focal necrosis or other abnormality in retinal histology was observed. Intravitreal caspofungin injection may be considered to be an alternative treatment for fungal endophthalmitis based on its antifungal activity, lower retinal toxicity, and lower elimination rate in the vitreous. More clinical data are needed to determine its potential role as primary therapy for fungal endophthalmitis.
Topics: Animals; Antifungal Agents; Aqueous Humor; Caspofungin; Dark Adaptation; Echinocandins; Electroretinography; Endophthalmitis; Eye Infections, Fungal; Half-Life; Intravitreal Injections; Lipopeptides; Rabbits; Retina; Vitreous Body
PubMed: 25246398
DOI: 10.1128/AAC.03324-14 -
Graefe's Archive For Clinical and... Dec 2015Increased expression of glial fibrillary acidic protein (GFAP) is a characteristic of gliotic activation (Müller cells and astrocytes) in the retina. This study...
PURPOSE
Increased expression of glial fibrillary acidic protein (GFAP) is a characteristic of gliotic activation (Müller cells and astrocytes) in the retina. This study assessed vitreous body GFAP levels in various forms of retinal pathology.
METHODS
This prospective study included 82 patients who underwent vitrectomy (46 retinal detachments (RDs), 13 macular hole (MHs), 15 epiretinal glioses (EGs), 8 organ donors). An established enzyme-linked immunosorbent assay (ELISA, SMI26) was used for quantification of GFAP.
RESULTS
The highest concentration of vitreous body GFAP in organ donors was 20 pg/mL and it was used as the cutoff. A significant proportion of patients suffering from RD (65 %) to EG (53 %) had vitreous body GFAP levels above this cutoff when compared to organ donors (0 %, p < 0.0001, p = 0.0194, respectively, Fisher's exact test) and MH (8 %, p < 0.0001, p = 0.0157, respectively). In RD and EG, vitreous body GFAP levels were correlated with axial length (R = 0.69, R = 0.52, p < 0.05 for both).
CONCLUSIONS
The data suggest that human vitreous body GFAP is a protein biomarker for glial activation in response to retinal pathologies. Vitreous body GFAP levels may be of interest as a surrogate outcome for experimental treatment strategies in translational studies.
Topics: Aged; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Glial Fibrillary Acidic Protein; Gliosis; Humans; Male; Middle Aged; Prospective Studies; Retinal Detachment; Retinal Diseases; Tissue Donors; Vitrectomy; Vitreous Body
PubMed: 26279003
DOI: 10.1007/s00417-015-3127-7