Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Macrophage recruitment in immune-privileged lens during capsule repair, necrotic fiber removal, and fibrosis.

ABSTRACT: Emerging evidence challenges the lens as an immune-privileged organ. Here, we provide a direct mechanism supporting a role of macrophages in lens capsule rupture repair. Posterior lens capsule rupture in a connexin 50 and aquaporin 0 double-knockout mouse model resulted in lens tissue extrusion into the vitreous cavity with formation of a "tail-like" tissue containing delayed regressed hyaloid vessels, fibrotic tissue and macrophages at postnatal (P) 15 days. The macrophages declined after P 30 days with M2 macrophages detected inside the lens. By P 90 days, the "tail-like" tissue completely disappeared and the posterior capsule rupture was sealed with thick fibrotic tissue. Colony-stimulating factor 1 (CSF-1) accelerated capsule repair, whereas inhibition of the CSF-1 receptor delayed the repair. Together, these results suggest that lens posterior rupture leads to the recruitment of macrophages delivered by the regression delayed hyaloid vessels. CSF-1-activated M2 macrophages mediate capsule rupture repair and development of fibrosis.

SUBMITTER: Li Y

PROVIDER: S-EPMC8188486 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

AGEs in human lens capsule promote the TGFβ2-mediated EMT of lens epithelial cells: implications for age-associated fibrosis.

Project description:Proteins in basement membrane (BM) are long-lived and accumulate chemical modifications during aging; advanced glycation endproduct (AGE) formation is one such modification. The human lens capsule is a BM secreted by lens epithelial cells. In this study, we have investigated the effect of aging and cataracts on the AGE levels in the human lens capsule and determined their role in the epithelial-to-mesenchymal transition (EMT) of lens epithelial cells. EMT occurs during posterior capsule opacification (PCO), also known as secondary cataract formation. We found age-dependent increases in several AGEs and significantly higher levels in cataractous lens capsules than in normal lens capsules measured by LC-MS/MS. The TGFβ2-mediated upregulation of the mRNA levels (by qPCR) of EMT-associated proteins was significantly enhanced in cells cultured on AGE-modified BM and human lens capsule compared with those on unmodified proteins. Such responses were also observed for TGFβ1. In the human capsular bag model of PCO, the AGE content of the capsule proteins was correlated with the synthesis of TGFβ2-mediated α-smooth muscle actin (αSMA). Taken together, our data imply that AGEs in the lens capsule promote the TGFβ2-mediated fibrosis of lens epithelial cells during PCO and suggest that AGEs in BMs could have a broader role in aging and diabetes-associated fibrosis.

| S-EPMC4854921 | biostudies-literature

The involvement of caspases in the process of nuclear removal during lens fiber cell differentiation.

Project description:The terminal differentiation of lens fiber cells involves elimination of their organelles, which must occur while still maintaining their functionality throughout a lifetime. Removal of non-nuclear organelles is accomplished through induction of autophagy following the spatiotemporal suppression of the PI3K/Akt signaling axis. However, blocking this pathway is not alone sufficient to induce removal of fiber cell nuclei. While the final steps in fiber cell nuclear elimination are highlighted by the appearance of TUNEL-positive nuclei, which are associated with activation of the lens-specific DNaseIIβ, there are many steps in the process that precede the appearance of double stranded DNA breaks. We showed that this carefully regulated process, including the early changes in nuclear morphology resulting in nuclear condensation, cleavage of lamin B, and labeling by pH2AX, is reminiscent of the apoptotic process associated with caspase activation. Multiple caspases are known to be expressed and activated during lens cell differentiation. In this study, we investigated the link between two caspase downstream targets associated with apoptosis, ICAD, whose cleavage by caspase-3 leads to activation of CAD, a DNase that can create both single- and double-stranded DNA cleavages, and lamin B, a primary component of the nuclear lamina. We discovered that the specific inhibition of caspase-3 activation prevents both lamin B and DNA cleavage. Inhibiting caspase-3 did not prevent nuclear condensation or removal of the nuclear membrane. In contrast, a pan-caspase inhibitor effectively suppressed condensation of fiber cell nuclei during differentiation. These studies provide evidence that caspases play an important role in the process of removing fiber cell nuclei during lens differentiation.

| S-EPMC10590423 | biostudies-literature

Surgical removal of inadvertent intralenticular sustained-release dexamethasone implant (ozurdex) and implant one-piece posterior capsule intraocular lens.

Project description:To report the therapeutic efficacy and results of an accidentally injected intralenticular sustained-release dexamethasone implant (Ozurdex) in a patient with macular edema secondary to diabetic macular edema. Dexamethasone intravitreal implant is an approved formulation in the management of macular edema. The most common adversarial effects are an elevation of intraocular pressure (IOP) and cataract, but the unintentional injection of the dexamethasone implant into the lens is a particularly rare event.We report a case of a 72-year-old man treated for resistant Diabetic macular edema (DME) with dexamethasone intravitreal implant (Ozurdex, Allergan, Inc., Irvine, CA, USA) in which the technique was complicated by accidental implantation into the lens body and review the management. The patient underwent phacoemulsification of the lens, removal of the Ozurdex, intravitreal Avastin injection, and implant of a one-piece lens in the posterior capsule.

| S-EPMC7866717 | biostudies-literature

Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly.

Project description:Lens epithelial cells and early lens fiber cells contain the typical complement of intracellular organelles. However, as lens fiber cells mature they must destroy their organelles, including nuclei, in a process that has remained enigmatic for over a century, but which is crucial for the formation of the organelle-free zone in the center of the lens that assures clarity and function to transmit light. Nuclear degradation in lens fiber cells requires the nuclease DNase IIβ (DLAD) but the mechanism by which DLAD gains access to nuclear DNA remains unknown. In eukaryotic cells, cyclin-dependent kinase 1 (CDK1), in combination with either activator cyclins A or B, stimulates mitotic entry, in part, by phosphorylating the nuclear lamin proteins leading to the disassembly of the nuclear lamina and subsequent nuclear envelope breakdown. Although most post-mitotic cells lack CDK1 and cyclins, lens fiber cells maintain these proteins. Here, we show that loss of CDK1 from the lens inhibited the phosphorylation of nuclear lamins A and C, prevented the entry of DLAD into the nucleus, and resulted in abnormal retention of nuclei. In the presence of CDK1, a single focus of the phosphonuclear mitotic apparatus is observed, but it is not focused in CDK1-deficient lenses. CDK1 deficiency inhibited mitosis, but did not prevent DNA replication, resulting in an overall reduction of lens epithelial cells, with the remaining cells possessing an abnormally large nucleus. These observations suggest that CDK1-dependent phosphorylations required for the initiation of nuclear membrane disassembly during mitosis are adapted for removal of nuclei during fiber cell differentiation.

| S-EPMC4199135 | biostudies-literature

Lens Epithelial Cells and Lens Cortical Fiber Cells

Project description:Total RNA was isolated from three separate populations of human lens epithelial cells and three matching populations of lens cortical fiber cells. All samples were analyzed on separate microarrays. Keywords: repeat sample

2005-02-15 | GSE2256 | GEO

Macrophage recruitment by fibrocystin-defective biliary epithelial cells promotes portal fibrosis in congenital hepatic fibrosis.

Project description:Congenital hepatic fibrosis (CHF) is a disease of the biliary epithelium characterized by bile duct changes resembling ductal plate malformations and by progressive peribiliary fibrosis, in the absence of overt necroinflammation. Progressive liver fibrosis leads to portal hypertension and liver failure; however, the mechanisms leading to fibrosis in CHF remain elusive. CHF is caused by mutations in PKHD1, a gene encoding for fibrocystin, a ciliary protein expressed in cholangiocytes. Using a fibrocystin-defective (Pkhd1(del4/del4)) mouse, which is orthologous of CHF, we show that Pkhd1(del4/del4) cholangiocytes are characterized by a ?-catenin-dependent secretion of a range of chemokines, including chemokine (C-X-C motif) ligands 1, 10, and 12, which stimulate bone marrow-derived macrophage recruitment. We also show that Pkhd1(del4/del4) cholangiocytes, in turn, respond to proinflammatory cytokines released by macrophages by up-regulating ?v?6 integrin, an activator of latent local transforming growth factor-?1. While the macrophage infiltrate is initially dominated by the M1 phenotype, the profibrogenic M2 phenotype increases with disease progression, along with the number of portal myofibroblasts. Consistent with these findings, clodronate-induced macrophage depletion results in a significant reduction of portal fibrosis and portal hypertension as well as of liver cysts.Fibrosis can be initiated by an epithelial cell dysfunction, leading to low-grade inflammation, macrophage recruitment, and collagen deposition; these findings establish a new paradigm for biliary fibrosis and represent a model to understand the relationship between cell dysfunction, parainflammation, liver fibrosis, and macrophage polarization over time.

| S-EPMC4764460 | biostudies-literature

Macrophage migration inhibitory factor regulates joint capsule fibrosis by promoting TGF-β1 production in fibroblasts.

Project description:Joint capsule fibrosis caused by excessive inflammation results in post-traumatic joint contracture (PTJC). Transforming growth factor (TGF)-β1 plays a key role in PTJC by regulating fibroblast functions, however, cytokine-induced TGF-β1 expression in specific cell types remains poorly characterized. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in inflammation- and fibrosis-associated pathophysiology. In this study, we investigated whether MIF can facilitate TGF-β1 production from fibroblasts and regulate joint capsule fibrosis following PTJC. Our data demonstrated that MIF and TGF-β1 significantly increased in fibroblasts of injured rat posterior joint capsules. Treatment the lesion sites with MIF inhibitor 4-Iodo-6-phenylpyrimidine (4-IPP) reduced TGF-β1 production and relieved joint capsule inflammation and fibrosis. In vitro, MIF facilitated TGF-β1 expression in primary joint capsule fibroblasts by activating mitogen-activated protein kinase (MAPK) (P38, ERK) signaling through coupling with membrane surface receptor CD74, which in turn affected fibroblast functions and promoted MIF production. Our results reveal a novel function of trauma-induced MIF in the occurrence and development of joint capsule fibrosis. Further investigation of the underlying mechanism may provide potential therapeutic targets for PTJC.

| S-EPMC8120472 | biostudies-literature

Characterizing molecular diffusion in the lens capsule.

Project description:The lens capsule compartmentalizes the cells of the avascular lens from other ocular tissues. Small molecules required for lens cell metabolism, such as glucose, salts, and waste products, freely pass through the capsule. However, the lens capsule is selectively permeable to proteins such as growth hormones and substrate carriers which are required for proper lens growth and development. We used fluorescence recovery after photobleaching (FRAP) to characterize the diffusional behavior of various sized dextrans (3, 10, 40, 150, and 250 kDa) and proteins endogenous to the lens environment (EGF, gammaD-crystallin, BSA, transferrin, ceruloplasmin, and IgG) within the capsules of whole living lenses. We found that proteins had dramatically different diffusion and partition coefficients as well as capsule matrix binding affinities than similar sized dextrans, but they had comparable permeabilities. We also found ionic interactions between proteins and the capsule matrix significantly influence permeability and binding affinity, while hydrophobic interactions had less of an effect. The removal of a single anionic residue from the surface of a protein, gammaD-crystallin [E107A], significantly altered its permeability and matrix binding affinity in the capsule. Our data indicated that permeabilities and binding affinities in the lens capsule varied between individual proteins and cannot be predicted by isoelectric points or molecular size alone.

| S-EPMC2849862 | biostudies-literature

Swivel haptics anterior capsule-fixated intraocular lens.

Project description:The purpose of the study is to report the feasibility of implantation of a new design of anterior capsule-fixated intraocular lens (IOL). The new IOL design is a foldable, hydrophilic, open-loop posterior chamber IOL with two extra polymethyl methacrylate swivel haptics created on the optic surface to capture the anterior capsulotomy after the IOL is implanted in the bag. In the pilot phase, the new IOL was implanted in 10 eyes of 10 patients of which 8 eyes underwent phacoemulsification and 2 eyes had laser cataract surgery. The mean spherical equivalent changed from *1.75 D to -0.75 D at 6 months. Postoperatively, from 1 week to 6 months, all eyes showed stable refraction and anterior chamber depth with no evidence of decentration. Subjective questionnaire revealed high patient satisfaction with no complaints of dysphotopsia. No intra- or postoperative complications such as swivel haptic breakage, iris chafing, pigment dispersion, postoperative uveitis, or endophthalmitis occurred in any of the eyes necessitating explantation of the IOL. The new IOL design was feasible to implant and provided satisfactory outcomes in terms of no dysphotopsias and stable effective lens position.

| S-EPMC6113843 | biostudies-literature

Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of Apoe-/- mice during disease regression.

Project description:Experimental models of atherosclerosis suggest that recruitment of monocytes into plaques drives the progression of this chronic inflammatory condition. Cholesterol-lowering therapy leads to plaque stabilization or regression in human atherosclerosis, characterized by reduced macrophage content, but the mechanisms that underlie this reduction are incompletely understood. Mice lacking the gene Apoe (Apoe-/- mice) have high levels of cholesterol and spontaneously develop atherosclerotic lesions. Here, we treated Apoe-/- mice with apoE-encoding adenoviral vectors that induce plaque regression, and investigated whether macrophage removal from plaques during this regression resulted from quantitative alterations in the ability of monocytes to either enter or exit plaques. Within 2 days after apoE complementation, plasma cholesterol was normalized to wild-type levels, and HDL levels were increased 4-fold. Oil red O staining and quantitative mass spectroscopy revealed that esterified cholesterol content was markedly reduced. Plaque macrophage content decreased gradually and was 72% lower than baseline 4 weeks after apoE complementation. Importantly, this reduction in macrophages did not involve migratory egress from plaques or CCR7, a mediator of leukocyte emigration. Instead, marked suppression of monocyte recruitment coupled with a stable rate of apoptosis accounted for loss of plaque macrophages. These data suggest that therapies to inhibit monocyte recruitment to plaques may constitute a more viable strategy to reduce plaque macrophage burden than attempts to promote migratory egress.

| S-EPMC3083793 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data