-
Molecular Vision 2023Increased inflammatory factor levels have been reported in the vitreous humor (VH) of diabetic retinopathy and neovascular age-related macular degeneration, ocular...
PURPOSE
Increased inflammatory factor levels have been reported in the vitreous humor (VH) of diabetic retinopathy and neovascular age-related macular degeneration, ocular diseases generally associated with the formation of new retinal blood vessels and leakage. However, the levels of inflammatory mediators are less known in retinal degeneration without neovascularization. Human retinitis pigmentosa (RP) and animal models of light-induced retinal degeneration (LIRD) share several features, such as photoreceptor death and retinal inflammation. Here, we aimed to determine the levels of inflammatory factors in the VH of the LIRD mouse model.
METHODS
LIRD was induced by exposing BALB/c mice to white light (15,000 lx, 2 h), and the mice were recovered for 2 days before analysis (n = 50 mice). We assessed retinal morphology using optical coherence tomography and hematoxylin and eosin staining; retinal cell viability was determined using terminal deoxynucleotidyl transferase dUTP nick-end labeling, and retinal responses were measured based on electroretinogram signals. Total retinal RNAs were extracted and subjected to RNA sequencing analysis. VH samples from control (n = 4) and LIRD mice (n = 9) were assayed in triplicate for a panel of four inflammatory mediators using the Simple Plex Cartridge on an Ella System.
RESULTS
Retinal degeneration, photoreceptor death, infiltration of microglia/macrophages into the photoreceptor layer, and loss of a- and b-waves were obviously detected after LIRD. RNA sequencing revealed that light damage (LD) led to the significant upregulation of inflammatory factors in mouse retinas. In the VH, LD increased the total protein concentration. Dramatic induction of CCL2 (~3000 fold) and IL6 (~10 fold) was detected in VH in response to LD. Increased but not significant levels of TNFα and IL1β were also detected in light-exposed VH.
CONCLUSIONS
Given that the LIRD model mimics RP pathogenesis in some aspects, these results suggest a causative link between retinal degeneration and VH inflammation in RP progression, and the increased CCL2 level in VH may reflect similar elevated CCL2 expression in the degenerative retina.
Topics: Mice; Humans; Animals; Retinal Degeneration; Vitreous Body; Retina; Retinitis Pigmentosa; Inflammation; Disease Models, Animal; Inflammation Mediators
PubMed: 38222454
DOI: No ID Found -
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 -
Science Advances Nov 2023Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment...
Choroidal melanoma, a common intraocular malignant tumor, relies on local radiotherapy and enucleation for treatment. However, cancer recurrence and visual impairment remain important challenges. Here, a therapeutic artificial vitreous body (AVB) hydrogel based on tetra-armed poly(ethylene glycol) was developed to control the recurrence of choroidal melanoma and preserve vision after vitrectomy. AVB loaded with melphalan (Mel) and anti-programmed cell death ligand-1 (αPDL1), was injected after surgical resection in the choroidal melanoma mouse model. Afterwards, the sequentially released Mel and αPDL1 from AVB could achieve a synergistic antitumor effect to inhibit tumor recurrence. AVB with similar physical properties to native vitreous body could maintain the normal structure and visual function of eye after vitrectomy, which has been evidenced by standard examinations of ophthalmology in the mouse model. Thus, the immunotherapeutic AVB may be a promising candidate as an infill biomaterial to assist surgical treatment of intraocular malignant tumors.
Topics: Animals; Mice; Vitreous Body; Vitrectomy; Hydrogels; Neoplasm Recurrence, Local; Melanoma; Choroid Neoplasms; Melphalan; Immunotherapy
PubMed: 37910617
DOI: 10.1126/sciadv.adh1582 -
Indian Journal of Ophthalmology Oct 2023Gaucher disease is a rare genetic disorder caused by a deficiency in the enzyme glucocerebrosidase, which impairs the body's ability to break down certain fats. This...
BACKGROUND
Gaucher disease is a rare genetic disorder caused by a deficiency in the enzyme glucocerebrosidase, which impairs the body's ability to break down certain fats. This leads to the accumulation of glucosyl sphingosine and glucosyl ceramide in the liver, spleen, and bone marrow. Gaucher disease has two major types: nonneuropathic (Type 1) and neuropathic (Type 2 and Type 3). Gaucher disease can have various ophthalmologic manifestations, particularly in Type 3, including posterior segment abnormalities, such as vitreous opacities, condensations, and/or preretinal white dots. We present a case of a patient with Gaucher disease Type 3 who had severe bilateral vitreous and extensive retinal deposits, leading to challenges during surgery.
PURPOSE
This video reports surgical outcomes for an uncommon ophthalmologic manifestation in a patient with Gaucher disease Type 3. We focus on the challenges and results of surgery for severe bilateral vitreous and extensive retinal deposits.
SYNOPSIS
A 16-year-old female patient with a history of Gaucher's disease since birth presented with a one-year history of blurred vision in both eyes. Her best-corrected visual acuity was 20/200 in the right eye and 20/100 in the left eye, as measured by Snellen's chart. Intraocular pressure was normal in both eyes, and anterior segment examinations were unremarkable. However, fundus evaluation revealed extensive vitreous deposits that obscured the details of the fundus. Additionally, an epiretinal membrane was observed over the macula in both eyes. Optical coherence tomography (OCT) confirmed the presence of deposits in the vitreous cavity and on the surface of the retina. The patient underwent pars plana vitrectomy with epiretinal membrane removal. A transconjunctival 23-G pars plana vitrectomy was performed to the extent possible. Multiple instruments were used to remove the fluffy vitreous deposits, as they were extremely adherent to the underlying surface of the retina, and brilliant blue dye was used to stain the internal limiting membrane. The epiretinal membrane and internal limiting membrane were removed from the macular area, and the entire cassette fluid was sent for histopathological examination to identify Gaucher cells. At one week postoperative, the patient's visual acuity improved to 20/125 in the right eye, and the fundus picture showed a cleared macular area. OCT showed a reduction in deposits over the retina. The histopathological examination revealed crumpled, barrel-like cytoplasm with an oval nucleus in a hemorrhagic background, suggestive of Gaucher cells.
HIGHLIGHTS
Early detection and treatment of ocular manifestations of Gaucher's disease are important to prevent permanent damage to vision. An ophthalmological assessment involving a dilated fundus examination and optical coherence tomography can facilitate early diagnosis and follow-up of ocular manifestations. Timely surgery may be required to preserve functional vision in patients with severe ocular disease.
VIDEO LINK
https://youtu.be/KR-kfgfDoqM.
Topics: Humans; Female; Adolescent; Gaucher Disease; Epiretinal Membrane; Retina; Vitrectomy; Retinal Degeneration; Tomography, Optical Coherence; Vision Disorders; Early Diagnosis
PubMed: 37787254
DOI: 10.4103/IJO.IJO_996_23 -
International Journal of Legal Medicine Sep 2023Post-mortem interval (PMI) is the cornerstone of the forensic field to investigate. The examination technique by seeing the changes in the body such as algor mortis,... (Review)
Review
BACKGROUND
Post-mortem interval (PMI) is the cornerstone of the forensic field to investigate. The examination technique by seeing the changes in the body such as algor mortis, rigor mortis, and livor mortis is a traditional technique in which accuracy is influenced by many factors. A biomolecular technique that uses microRNA (miRNA) biomarkers is developing because miRNA has good stability than other RNA, so it meets the requirements to be used for PMI estimation.
METHOD
Following the PRISMA guidelines, journals were taken from 5 databases: Scopus, Science Direct, PubMed, Embase, and Springer. The review was carried out by two people. Inclusion criteria in this review are original research, published in the last 10 years, discussing miRNA as a biomarker for PMI estimation, and free full access. While exclusion criteria are not original research and not using English.
RESULT
Eighteen journals were reviewed in this study. The study was conducted using test animals (rats) and human samples with tissue sources taken from the liver, skeletal muscle, blood, bone, heart, skin, saliva, semen, brain, lung, vitreous humor, spleen, and kidney. miRNA expression levels after death showed different results based on miRNA target, tissue source, and others.
DISCUSSION
The results of each study are different due to the use of different types of miRNA targets and tissue sources. miRNA has great potential to estimate PMI in forensic science, but it is necessary to control the influencing factors to obtain an accurate conclusion.
Topics: Humans; Animals; Rats; MicroRNAs; Autopsy; Postmortem Changes; Forensic Medicine; Forensic Sciences; Biomarkers
PubMed: 37253884
DOI: 10.1007/s00414-023-03015-z -
Experimental Eye Research Apr 2024Extracellular vesicles (EVs) are released as highly stable lipid bilayer particles carrying proteins, lipids, glycans and miRNAs. The contents of EVs vary based on the... (Review)
Review
Extracellular vesicles (EVs) are released as highly stable lipid bilayer particles carrying proteins, lipids, glycans and miRNAs. The contents of EVs vary based on the cellular origin, biogenesis route and the functional state of the cell suggesting certain diseased conditions. A growing body of evidence show that EVs carry important molecules implicated in the development and progression of ophthalmic diseases. EVs associated with ophthalmic diseases are mainly carried by one of the three ocular biofluids which include tears, aqueous humor and vitreous humor. This review summarizes the list of EV derived biomarkers identified thus far in ocular fluids for ophthalmic disease diagnosis. Further, the methods used for sample collection, sample volume and the sample numbers used in these studies have been highlighted. Emphasis has been given to describe the EV isolation and the characterization methods used, EV size profiled and the EV concentrations analyzed by these studies, thus providing a roadmap for future EV biomarker studies in ocular fluids.
Topics: Extracellular Vesicles; Biomarkers; MicroRNAs; Proteins; Body Fluids
PubMed: 38401855
DOI: 10.1016/j.exer.2024.109831 -
Forensic Science International Sep 2023Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality worldwide. The patients' and injuries' heterogeneity associated with TBI, alongside...
BACKGROUND
Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality worldwide. The patients' and injuries' heterogeneity associated with TBI, alongside with its variable clinical manifestations, make it challenging to make diagnosis and predict prognosis. Therefore, the identification of reliable prognostic markers would be relevant both to support clinical decision-making and forensic evaluation of polytraumatic deaths and cases of medical malpractice. This pilot study aimed to evaluate some of the main biomarkers specific for brain damage in sTBI and mmTBI deaths in samples of vitreous humor (VH) in order to verify whether predictors of prognosis in TBI can be found in this matrix.
METHODS
VH were obtained from both eyes (right and left) of 30 cadavers (20 sTBI and 10 mmTBI) and analysed. These factors were evaluated: NSE (neuron-specific enolase), S100 calcium-binding protein (S100), glial fibrillary acidic protein (GFAP), Brain-derived neurotrophic factor (BDNF), Copeptin, Interleukin 6 (IL-6), Ferritin, Lactate dehydrogenase (LDH), C-Reactive Protein (CRP), Procalcitonin (PCT), Glucose and Neutrophil gelatinase-associated lipocalin (N-Gal).
RESULTS
Four of the analysed proteins (LDH, ferritin, S100 and NSE) proved to be particularly promising. In particular, logistic regression analysis found a good discriminatory power.
CONCLUSIONS
Given the peculiarity of the matrix and the poor standardization of the sampling, such promising results need to be furtherly investigated in serum before being implemented in the forensic practice.
Topics: Humans; Pilot Projects; Vitreous Body; S100 Calcium Binding Protein beta Subunit; Brain Injuries, Traumatic; Biomarkers; Glial Fibrillary Acidic Protein; Ferritins
PubMed: 37467521
DOI: 10.1016/j.forsciint.2023.111782 -
Biomedicines Dec 2023In the early stages of Alzheimer-Perusini's disease (AD), individuals often experience vision-related issues such as color vision impairment, reduced contrast... (Review)
Review
In the early stages of Alzheimer-Perusini's disease (AD), individuals often experience vision-related issues such as color vision impairment, reduced contrast sensitivity, and visual acuity problems. As the disease progresses, there is a connection with glaucoma and age-related macular degeneration (AMD) leading to retinal cell death. The retina's involvement suggests a link with the hippocampus, where most AD forms start. A thinning of the retinal nerve fiber layer (RNFL) due to the loss of retinal ganglion cells (RGCs) is seen as a potential AD diagnostic marker using electroretinography (ERG) and optical coherence tomography (OCT). Amyloid beta fragments (Aβ), found in the eye's vitreous and aqueous humor, are also present in the cerebrospinal fluid (CSF) and accumulate in the retina. Aβ is known to cause tau hyperphosphorylation, leading to its buildup in various retinal layers. However, diseases like AD are now seen as mixed proteinopathies, with deposits of the prion protein (PrP) and α-synuclein found in affected brains and retinas. Glial cells, especially microglial cells, play a crucial role in these diseases, maintaining immunoproteostasis. Studies have shown similarities between retinal and brain microglia in terms of transcription factor expression and morphotypes. All these findings constitute a good start to achieving better comprehension of neurodegeneration in both the eye and the brain. New insights will be able to bring the scientific community closer to specific disease-modifying therapies.
PubMed: 38137479
DOI: 10.3390/biomedicines11123258 -
Heliyon Jan 2024N6-methyladenosine (mA) modification, as the most common modification method in eukaryotes, is widely involved in numerous physiological and pathological processes, such... (Review)
Review
N6-methyladenosine (mA) modification, as the most common modification method in eukaryotes, is widely involved in numerous physiological and pathological processes, such as embryonic development, malignancy, immune regulation, and premature aging. Under pathological conditions of ocular diseases, changes in mA modification and its metabolism can be detected in aqueous and vitreous humor. At the same time, an increasing number of studies showed that mA modification is involved in the normal development of eye structures and the occurrence and progress of many ophthalmic diseases, especially ocular neovascular diseases, such as diabetic retinopathy, age-related macular degeneration, and melanoma. In this review, we summarized the latest progress regarding mA modification in ophthalmic diseases, changes in mA modification-related enzymes in various pathological states and their upstream and downstream regulatory networks, provided new prospects for mA modification in ophthalmic diseases and new ideas for clinical diagnosis and treatment.
PubMed: 38192819
DOI: 10.1016/j.heliyon.2023.e23668