-
Indian Journal of Ophthalmology Dec 2018Twenty-five percent of diabetes-related vision loss stems from complications of proliferative diabetic retinopathy (PDR). Panretinal photocoagulation has been the... (Review)
Review
Twenty-five percent of diabetes-related vision loss stems from complications of proliferative diabetic retinopathy (PDR). Panretinal photocoagulation has been the preferred treatment of high-risk PDR for decades and more recently intravitreal injections of drugs that inhibit the actions of vascular endothelial growth factor have become popular. But despite these treatments PDR may progress uncontrollably to advanced pathologies such as traction retinal detachments (TRDs), combined traction/rhegmatogenous retinal detachments (TRD/RRDs), vitreous hemorrhages, rubeosis iridis, and traction maculopathies, which produce mild-to-severe loss of vision. TDR have long been the most common indication for PDR-related vitreoretinal surgery. Vitrectomy surgery is indicated for recent (<6 months duration) TRD involving the macula, progressive TRD that threatens the macula, and recent data suggest that chronic macula-involving TRDs (>6 months duration) may also benefit. Combined TRD/RRD represents a particularly challenging surgical condition but advances in surgical instrumentation, dissection techniques, and post-operative tamponade have produced excellent success rates. The recent development of small-gauge vitrectomy systems has persuaded most surgeons to switch platforms since these appear to produce shorter surgical times and quicker post-operative recoveries. Pre-operative injections of bevacizumab are frequently administered for persistent neovascularization to facilitate surgical dissection of pre-retinal fibrosis and reduce the incidence of post-operative hemorrhages. Recent trends toward earlier surgical intervention and expanded indications are likely to continue as surgical instrumentation and techniques are further developed.
Topics: Angiogenesis Inhibitors; Diabetic Retinopathy; Disease Management; Fluorescein Angiography; Fundus Oculi; Humans; Intravitreal Injections; Retinal Detachment; Tomography, Optical Coherence; Vascular Endothelial Growth Factor A; Visual Acuity; Vitrectomy
PubMed: 30451175
DOI: 10.4103/ijo.IJO_1217_18 -
Frontiers in Cell and Developmental... 2023Detachment from the extracellular matrix (ECM) is the first step of the metastatic cascade. It is a regulated process involving interaction between tumor cells and...
Detachment from the extracellular matrix (ECM) is the first step of the metastatic cascade. It is a regulated process involving interaction between tumor cells and tumor microenvironment (TME). Iron is a key micronutrient within the TME. Here, we explored the role of iron in the ability of ovarian cancer cells to successfully detach from the ECM. HEY and PEO1 ovarian cancer cells were grown in 3D conditions. To mimic an iron rich TME, culture media were supplemented with 100 μM Fe. Cell mortality was evaluated by cytofluorimetric assay. The invasive potential of tumor spheroids was performed in Matrigel and documented with images and time-lapses. Iron metabolism was assessed by analyzing the expression of CD71 and FtH1, and by quantifying the intracellular labile iron pool (LIP) through Calcein-AM cytofluorimetric assay. Ferroptosis was assessed by quantifying mitochondrial reactive oxygen species (ROS) and lipid peroxidation through MitoSOX and BODIPY-C11 cytofluorimetric assays, respectively. Ferroptosis markers GPX4 and VDAC2 were measured by Western blot. knockdown was performed by using siRNA. To generate spheroids, HEY and PEO1 cells prevent LIP accumulation by upregulating FtH1. 3D HEY moderately increases FtH1, and LIP is only slightly reduced. 3D PEO1upregulate FtH1 and LIP results significantly diminished. HEY tumor spheroids prevent iron import downregulating CD71, while PEO1 cells strongly enhance it. Intracellular ROS drop down during the 2D to 3D transition in both cell lines, but more significantly in PEO1 cells. Upon iron supplementation, PEO1 cells continue to enhance CD71 and FtH1 without accumulating the LIP and ROS and do not undergo ferroptosis. HEY, instead, accumulate LIP, undergo ferroptosis and attenuate their sphere-forming ability and invasiveness. knockdown significantly reduces the generation of PEO1 tumor spheroids, although without sensitizing them to ferroptosis. Iron metabolism reprogramming is a key event in the tumor spheroid generation of ovarian cancer cells. An iron-rich environment impairs the sphere-forming ability and causes cell death only in ferroptosis sensitive cells. A better understanding of ferroptosis sensitivity could be useful to develop effective treatments to kill ECM-detached ovarian cancer cells.
PubMed: 38033861
DOI: 10.3389/fcell.2023.1272667 -
MBio May 2021Gram-negative bacteria have a unique cell envelope with a lipopolysaccharide-containing outer membrane that is tightly connected to a thin layer of peptidoglycan. The...
Gram-negative bacteria have a unique cell envelope with a lipopolysaccharide-containing outer membrane that is tightly connected to a thin layer of peptidoglycan. The tight connection between the outer membrane and peptidoglycan is needed to maintain the outer membrane as an impermeable barrier for many toxic molecules and antibiotics. such as covalently attach the abundant outer membrane-anchored lipoprotein Lpp (Braun's lipoprotein) to tripeptides in peptidoglycan, mediated by the transpeptidases LdtA, LdtB, and LdtC. LdtD and LdtE are members of the same family of ld-transpeptidases but they catalyze a different reaction, the formation of 3-3 cross-links in the peptidoglycan. The function of the sixth homologue in , LdtF, remains unclear, although it has been shown to become essential in cells with inhibited lipopolysaccharide export to the outer membrane. We now show that LdtF hydrolyzes the Lpp-peptidoglycan linkage, detaching Lpp from peptidoglycan, and have renamed LdtF to peptidoglycan -iaminopimelic acid rotein midase (DpaA). We show that the detachment of Lpp from peptidoglycan is beneficial for the cell under certain stress conditions and that the deletion of allows frequent transposon inactivation in the () gene, whose product downregulates lipopolysaccharide biosynthesis. DpaA-like proteins have characteristic sequence motifs and are present in many Gram-negative bacteria, of which some have no Lpp, raising the possibility that DpaA has other substrates in these species. Overall, our data show that the Lpp-peptidoglycan linkage in is more dynamic than previously appreciated. Gram-negative bacteria have a complex cell envelope with two membranes and a periplasm containing the peptidoglycan layer. The outer membrane is firmly connected to the peptidoglycan by highly abundant proteins. The outer membrane-anchored Braun's lipoprotein (Lpp) is the most abundant protein in , and about one-third of the Lpp molecules become covalently attached to tripeptides in peptidoglycan. The attachment of Lpp to peptidoglycan stabilizes the cell envelope and is crucial for the outer membrane to function as a permeability barrier for a range of toxic molecules and antibiotics. So far, the attachment of Lpp to peptidoglycan has been considered to be irreversible. We have now identified an amidase, DpaA, which is capable of detaching Lpp from peptidoglycan, and we show that the detachment of Lpp is important under certain stress conditions. DpaA-like proteins are present in many Gram-negative bacteria and may have different substrates in these species.
Topics: Amidohydrolases; Diaminopimelic Acid; Escherichia coli; Escherichia coli Proteins; Lipoproteins; Peptidoglycan
PubMed: 33947763
DOI: 10.1128/mBio.00836-21 -
The Journal of Analytical Psychology Jun 2021This paper attempts to read the psychological and emotional impact of the COVID-19 pandemic through the archetypal images contained in patients' dreams. In these dreams,...
This paper attempts to read the psychological and emotional impact of the COVID-19 pandemic through the archetypal images contained in patients' dreams. In these dreams, symbols related to the power of nature and to extreme danger are paired with feelings of detachment that seem to point to a traumatic dissociation, due to the archetypal experience that erupts in familiar surroundings. Through the humanization of the ineffable experience, dissociation, which in the beginning of the pandemic showed in high levels of anxiety, panic attacks and depersonalization, can be transformed into the overview needed for the search for meaning. The container for this process of transformation is the analyst, the real, virtual or imagined one, and his or her ability to relate and feel.
Topics: Adult; COVID-19; Dreams; Humans; Professional-Patient Relations; Psychoanalytic Interpretation; Psychoanalytic Therapy; Psychotherapeutic Processes
PubMed: 34231897
DOI: 10.1111/1468-5922.12676 -
Retinal Cases & Brief Reports May 2022To illustrate with multimodal imaging a case of HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) complicated by bilateral multifocal serous retinal...
PURPOSE
To illustrate with multimodal imaging a case of HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) complicated by bilateral multifocal serous retinal detachments, subretinal exudation, and papilledema.
METHODS
Case report. Fundus photography, spectral domain optical coherence tomography (SD-OCT), fluorescein angiography, and indocyanine green angiography were performed at presentation and the day after. We also present the SD-OCT follow-up at 8 days, 1 year, and 4 years.
RESULTS
A 25-year-old 5-month-pregnant Guinean woman complained about decreased visual acuity in the right eye. Eye fundus and multimodal imaging were abnormal in both eyes. Spectral domain optical coherence tomography showed the presence of multifocal serous retinal detachments, subretinal deposits, and intraretinal cysts. Indocyanin green angiography revealed an irregular choroidal perfusion and localized choroidal ischemia. Spectral domain optical coherence tomography also provided assessment of retinal changes during the long-term follow-up, showing tissue damage in the outer retina.
CONCLUSION
Serous retinal detachments during pregnancy can be the leading sign of HELLP syndrome-a potentially life-threatening condition. Spectral domain optical coherence tomography is a noninvasive and useful tool for its diagnosis and follow-up. ICG is important to confirm the choroidal ischemia and choroidal vascular abnormalities, underlying conditions leading to main sign of HELLP syndrome in the eye.
Topics: Central Serous Chorioretinopathy; Choroid Diseases; Female; Fluorescein Angiography; HELLP Syndrome; Humans; Multimodal Imaging; Pregnancy; Retinal Detachment; Retinal Diseases; Tomography, Optical Coherence
PubMed: 32028449
DOI: 10.1097/ICB.0000000000000970 -
Science Robotics Apr 2021Although there have been notable advances in adhesive materials, the ability to program attaching and detaching behavior in these materials remains a challenge. Here, we...
Although there have been notable advances in adhesive materials, the ability to program attaching and detaching behavior in these materials remains a challenge. Here, we report a borate ester polymer hydrogel that can rapidly switch between adhesive and nonadhesive states in response to a mild electrical stimulus (voltages between 3.0 and 4.5 V). This behavior is achieved by controlling the exposure and shielding of the catechol group through water electrolysis-induced reversible cleavage and reformation of the borate ester moiety. By switching the electric field direction, the hydrogel can repeatedly attach to and detach from various surfaces with a response time as low as 1 s. This programmable attaching/detaching strategy provides an alternative approach for robot climbing. The hydrogel is simply pasted onto the moving parts of climbing robots without complicated engineering and morphological designs. Using our hydrogel as feet and wheels, the tethered walking robots and wheeled robots can climb on both vertical and inverted conductive substrates (i.e., moving upside down) such as stainless steel and copper. Our study establishes an effective route for the design of smart polymer adhesives that are applicable in intelligent devices and an electrochemical strategy to regulate the adhesion.
PubMed: 34043565
DOI: 10.1126/scirobotics.abe1858 -
Medical Hypotheses Nov 2020The limiting step in cancer prevention is a lack of understanding of cancer biology. This limitation is exacerbated by a focus on the dominant somatic mutation theory...
The limiting step in cancer prevention is a lack of understanding of cancer biology. This limitation is exacerbated by a focus on the dominant somatic mutation theory (that driver mutations cause cancer) with little consideration of alternative theories of carcinogenesis. The recently proposed detached pericyte hypothesis explains many puzzling phenomena in cancer biology for which the somatic mutation theory offers no obvious explanation. These puzzling phenomena include foreign-body tumorigenesis, the link between denervation and cancer, tumors in transgenic mice that lack the inducing mutation, and non-genotoxic carcinogens. The detached pericyte hypothesis postulates that (1) a carcinogen or chronic inflammation causes pericytes to detach from blood cell walls, (2) some detached pericytes develop into myofibroblasts which alter the extracellular matrix (3) some detached pericytes develop into mesenchymal stem cells, (4) some of the mesenchymal stem cells adhere to the altered extracellular matrix (5) the altered extracellular matrix disrupts regulatory controls, causing the adjacent mesenchymal stem cells to develop into tumors. Results from experimental studies support the detached pericyte hypothesis. If the detached pericyte hypothesis is correct, pericytes should play a key role in metastasis - a testable prediction. Recent experimental results confirm this prediction and motivate a proposed experiment to partially test the detached pericyte hypothesis. If the detached pericyte hypothesis is correct, it could lead to new strategies for cancer prevention.
Topics: Animals; Carcinogenesis; Mesenchymal Stem Cells; Mice; Mice, Transgenic; Myofibroblasts; Pericytes
PubMed: 32758893
DOI: 10.1016/j.mehy.2020.110056 -
Graefe's Archive For Clinical and... Mar 2020The key to successful management of rhegmatogenous retinal detachment (RRD) is to find and seal all of the retinal breaks, and the two main surgical techniques used to... (Review)
Review
The key to successful management of rhegmatogenous retinal detachment (RRD) is to find and seal all of the retinal breaks, and the two main surgical techniques used to achieve this are scleral bucking (SB) or pars plana vitrectomy (PPV). Techniques for SB have remained mostly unchanged for the last 60 years, whilst PPV techniques and instruments have developed substantially over that time and have greatly contributed to increased success rate for types and configurations of retinal detachments unsuitable or difficult to manage with buckling alone. However, there is a growing dependency to rely on PPV as the sole and only approach for repair of all types of retinal detachment, such that some centres are no longer offering training in scleral buckling. There are also many studies comparing SB with PPV, but many of these lack information on the type, technique or rationale for deployment of the buckle. Many studies deploy the same scleral buckle technique without customising it to the type, position or number of tears being treated. Scleral buckling is not a one-size-fits-all technique. It requires careful patient selection and careful buckle selection and orientation tailored to the tear(s) to ensure success. When used appropriately, it is a simple and highly effective technique, particularly for retinal dialyses, round retinal hole detachments and selected cases of retinal detachment associated with horseshoe retinal tears. There is no doubt that for some more complex cases, such as multiple large breaks, giant retinal tears, bullous detachments and cases complicated by proliferative retinopathy, PPV offers a safer and more effective management. However, SB remains an important and relevant surgical technique, and for the right cases, the results can be superior to PPV with reduced comorbidity.
Topics: History, 20th Century; History, 21st Century; Humans; Retinal Detachment; Scleral Buckling
PubMed: 31828426
DOI: 10.1007/s00417-019-04562-1 -
Ophthalmic Surgery, Lasers & Imaging... Sep 2022
Topics: Arthritis; Connective Tissue Diseases; Eye Diseases, Hereditary; Hearing Loss, Sensorineural; Humans; Retinal Detachment
PubMed: 36107624
DOI: 10.3928/23258160-20220815-03 -
Ophthalmology. Retina Jan 2024Scleral buckling has been a reliable treatment option in the repair of primary rhegmatogenous retinal detachments. Occasionally, patients require scleral buckles (SBs)... (Observational Study)
Observational Study
PURPOSE
Scleral buckling has been a reliable treatment option in the repair of primary rhegmatogenous retinal detachments. Occasionally, patients require scleral buckles (SBs) to be removed for various reasons. While outcomes of SB removal have been investigated in this subset of patients, there has not been any large patient series to reach any conclusions. Long-term sequelae of SB removal are debated in the literature, specifically around the risk of redetachment.
DESIGN
We performed a retrospective, observational study to evaluate the clinical indications for, and outcomes of, SB removal.
PARTICIPANTS
No control patients in this retrospective, observational study.
METHODS
Eighty-six individuals with a history of SB removal from June 1, 2000, to January 1, 2021, were followed from a large academic center and a private, retina-only practice in Chicago. Exclusion criteria were age of < 18 years and unplanned or self-explanted SB removal.
MAIN OUTCOME MEASURES
Data extracted included patient symptoms before SB removal, indications for removal, resolution of symptoms following removal, rate of redetachment, and rate of additional ocular surgery. Secondary outcomes included identifying factors associated with poorer outcomes.
RESULTS
Eighty-six eyes with history of SB removal were included with an average follow-up of 4 years. Approximately 60% were males and the mean age at the time of SB removal was 59 years. Leading indications for removal were exposure (61.63%), infection (20.93%), and diplopia/strabismus (19.77%). The average time from SB placement to removal was 12.28 ± 11.16 years. Most patients requiring SB removal presented with symptoms, specifically of pain and discomfort (65.12%), diplopia (22.09%), and drainage/discharge (18.60%). Of these patients, 86.59% experienced symptom resolution following SB removal. Notably, 6.56% (4 eyes) of all eyes with at least 1 year of follow-up experienced a redetachment requiring surgery. Within this subset, the average time from SB placement to removal was 2.05 ± 2.01 years and time to redetachment following removal was 15.95 ± 25.71 months. Nine percent of all eyes required additional strabismus or oculoplastic surgery.
CONCLUSIONS
Scleral buckle removal provides a high rate of symptomatic relief and low risk of subsequent detachment. Nevertheless, close monitoring is warranted to monitor for recurrent retinal detachments.
FINANCIAL DISCLOSURE(S)
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Topics: Male; Humans; Middle Aged; Adolescent; Female; Scleral Buckling; Retinal Detachment; Diplopia; Retrospective Studies; Treatment Outcome; Visual Acuity; Strabismus
PubMed: 37531997
DOI: 10.1016/j.oret.2023.07.029