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Brazilian Journal of Biology = Revista... 2021Mammals have a limited capacity to regenerate their tissues and organs. One of the mechanisms associated with natural regeneration is dedifferentiation. Several small...
Mammals have a limited capacity to regenerate their tissues and organs. One of the mechanisms associated with natural regeneration is dedifferentiation. Several small molecules such as vitamin C and growth factors could improve reprogramming efficiency. In this study, the NTERA2-D1 (NT2) cells were induced towards differentiation (NT2-RA) with 10-5 M retinoic acid (RA) for three days and then subjected to various amounts of vitreous humor (VH). Results show that the growth rate of these cells was reduced, while this rate was partly restored upon treatment with VH (NT2-RA-VH). Cell cycle analysis with PI method also showed that the numbers of cells at the S phase of the cell cycle in these cells were increased. The levels of SSEA3 and TRA-1-81 antigens in NT2-RA were dropped but they increased in NT2- RA-VH to a level similar to the NT2 cells. The level of SSEA1 had an opposite pattern. Expression of OCT4 gene dropped after RA treatment, but it was recovered in NT2-RA-VH cells. In conclusion, we suggest VH as a potent mixture for improving the cellular reprogramming leading to dedifferentiation.
Topics: Cell Dedifferentiation; Cell Differentiation; Cell Division; Cell Line; Cell Proliferation; Humans; Tretinoin; Tumor Cells, Cultured; Vitreous Body
PubMed: 34817042
DOI: 10.1590/1519-6984.250151 -
Mediators of Inflammation 2012Non infectious vitreous inflammation is often vision threatening and can be associated with potentially life-threatening systemic conditions. Treatment is often... (Review)
Review
Non infectious vitreous inflammation is often vision threatening and can be associated with potentially life-threatening systemic conditions. Treatment is often challenging as it involves systemic medications that can be associated with adverse effects. The classes of drugs are ever expanding and include corticosteroids, antimetabolites, alkylating agents, T-cell and calcineurin agents, biologic agents, and interferons. Each class of systemic therapy for non-infectious vitreous inflammation is reviewed. We discuss the mechanisms of action, usual clinical dosages, the specific conditions that are treated, the adverse effects, and usual course of treatment for each class of therapy.
Topics: Adrenal Cortex Hormones; Antimetabolites; Biological Products; Humans; Inflammation; Interferons; Vitreous Body
PubMed: 23028205
DOI: 10.1155/2012/936721 -
Translational Vision Science &... Feb 2020Proliferative vitreoretinopathy (PVR) occurs in 5%-10% of rhegmatogenous retinal detachment cases and is the principle cause for failure of retinal reattachment surgery.... (Review)
Review
PURPOSE
Proliferative vitreoretinopathy (PVR) occurs in 5%-10% of rhegmatogenous retinal detachment cases and is the principle cause for failure of retinal reattachment surgery. Although there are a number of surgical adjunctive agents available for preventing the development of PVR, all have limited efficacy. Discovering predictive molecular biomarkers to determine the probability of PVR development after retinal reattachment surgery will allow better patient stratification for more targeted drug evaluations.
METHODS
Narrative literature review.
RESULTS
We provide a summary of the inflammatory and fibrogenic factors found in ocular fluid samples during the development of retinal detachment and PVR and discuss their possible use as molecular PVR predictive biomarkers.
CONCLUSIONS
Studies monitoring the levels of the above factors have found that few if any have predictive biomarker value, suggesting that widening the phenotype of potential factors and a combinatorial approach are required to determine predictive biomarkers for PVR.
TRANSLATIONAL RELEVANCE
The identification of relevant biomarkers relies on an understanding of disease signaling pathways derived from basic science research. We discuss the extent to which those molecules identified as biomarkers and predictors of PVR relate to disease pathogenesis and could function as useful disease predictors. (http://www.umin.ac.jp/ctr/ number, UMIN000005604).
Topics: Biomarkers; Humans; Retinal Detachment; Risk Factors; Vitreoretinopathy, Proliferative; Vitreous Body
PubMed: 32742753
DOI: 10.1167/tvst.9.3.23 -
Investigative Ophthalmology & Visual... May 2017To review the usefulness of local and systemic inflammatory biomarkers of diabetic retinopathy (DR) to implement a more personalized treatment. (Review)
Review
PURPOSE
To review the usefulness of local and systemic inflammatory biomarkers of diabetic retinopathy (DR) to implement a more personalized treatment.
METHODS
An integrated research (from ophthalmologist and diabetologist point of view) of most significant literature on serum, vitreous, and aqueous humor (AH) biochemical biomarkers related to inflammation at early and advanced stages of DR (including diabetic macular edema [DME] and proliferative DR) was performed. Moreover, novel imaging retinal biomarkers of local "inflammatory condition" were described.
RESULTS
Multiple inflammatory cytokines and chemokines are increased in DR in both serum as well as in the eye (vitreous and AH). Nevertheless, local rather than systemic production of proinflammatory cytokines seems more relevant in the pathogenesis of both DR and DME. In the eye, retinal glia cells (macroglia and microglia) together with RPE are major sources of proinflammatory and angiogenic modulators. Retinal imaging allows for noninvasive clinical evaluation of retinal inflammatory response induced by diabetes mellitus.
CONCLUSIONS
Proinflammatory cytokines/chemokines play an essential role in the pathogenesis of DR. Therefore, circulating biomarkers and retinal imaging aimed at assessing inflammation have emerged as useful tools for monitoring the onset and progression of DR. In addition, "liquid biopsy" of AH seems a good option in patients with advanced stages of DR requiring intravitreous injections. This strategy may permit us to implement a more personalized treatment with better visual function outcome. Further evaluation and validation of circulating and local biomarkers, as well as multimodal imaging is needed to gain new insights into this issue.
Topics: Aqueous Humor; Biomarkers; Cytokines; Diabetic Retinopathy; Disease Progression; Humans; Inflammation; Vitreous Body
PubMed: 28510630
DOI: 10.1167/iovs.17-21769 -
Cells May 2022Retinoblastoma (Rb) is a pediatric intraocular malignancy that is proposed to originate from maturing cone cell precursors in the developing retina. The molecular...
Integrated Analysis of Cancer Tissue and Vitreous Humor from Retinoblastoma Eyes Reveals Unique Tumor-Specific Metabolic and Cellular Pathways in Advanced and Non-Advanced Tumors.
Retinoblastoma (Rb) is a pediatric intraocular malignancy that is proposed to originate from maturing cone cell precursors in the developing retina. The molecular mechanisms underlying the biological and clinical behaviors are important to understand in order to improve the management of advanced-stage tumors. While the genetic causes of Rb are known, an integrated understanding of the gene expression and metabolic processes in tumors of human eyes is deficient. By integrating transcriptomic profiling from tumor tissues and metabolomics from tumorous eye vitreous humor samples (with healthy, age-matched pediatric retinae and vitreous samples as controls), we uncover unique functional associations between genes and metabolites. We found distinct gene expression patterns between clinically advanced and non-advanced Rb. Global metabolomic analysis of the vitreous humor of the same Rb eyes revealed distinctly altered metabolites, indicating how tumor metabolism has diverged from healthy pediatric retina. Several key enzymes that are related to cellular energy production, such as hexokinase 1, were found to be reduced in a manner corresponding to altered metabolites; notably, a reduction in pyruvate levels. Similarly, E2F2 was the most significantly elevated E2F family member in our cohort that is part of the cell cycle regulatory circuit. Ectopic expression of the wild-type gene in the Rb-null Y79 and WERI-Rb1 cells rescued hexokinase 1 expression, while E2F2 levels were repressed. In an additional set of Rb tumor samples and pediatric healthy controls, we further validated differences in the expression of HK1 and E2F2. Through an integrated omics analysis of the transcriptomics and metabolomics of Rb, we uncovered a significantly altered tumor-specific metabolic circuit that reduces its dependence on glycolytic pathways and is governed by Rb1 and HK1.
Topics: Child; Hexokinase; Humans; Retinal Neoplasms; Retinoblastoma; Retinoblastoma Protein; Vitreous Body
PubMed: 35626705
DOI: 10.3390/cells11101668 -
International Ophthalmology Clinics 2014The identification of an infectious or noninfectious uveitis syndrome is important to determine the range of therapeutic and prognostic implications of that disease... (Review)
Review
The identification of an infectious or noninfectious uveitis syndrome is important to determine the range of therapeutic and prognostic implications of that disease entity. Diagnostic dilemmas arise with atypical history, atypical clinical presentations, inconclusive diagnostic workup, and persistent or worsened inflammation despite appropriate immunosuppression. More invasive intraocular testing is indicated in these situations particularly in infectious uveitis where a delay in treatment may result in worsening of the patient’s disease and a poor visual outcome. Laboratory analysis of vitreous fluid via diagnostic pars plana vitrectomy is an important technique in the diagnostic armamentarium, but the most important aspects of sample collection include rapid processing, close coordination with an ophthalmic pathology laboratory, and directed testing on this limited collected sample. Culture and staining has utility in bacterial, fungal, and nocardial infection. Polymerase chain reaction (PCR) analysis has shown promising results for bacterial endophthalmitis and infection with mycobacterium tuberculosis whereas PCR testing for viral retinitides and ocular toxoplasmosis has a more established role. Antibody testing is appropriate for toxoplasmosis and toxocariasis, and may be complementary to PCR for viral retinitis. Masquerade syndromes represent neoplastic conditions that clinically appear as infectious or inflammatory conditions and should be considered as part of the differential diagnosis. Diagnostic vitrectomy and chorioretinal biopsy are thus critical tools for the management of patients in whom an infectious etiology of uveitis is suspected.
Topics: Diagnosis, Differential; Diagnostic Techniques, Ophthalmological; Eye Infections; Humans; Reproducibility of Results; Uveitis; Vitrectomy; Vitreous Body
PubMed: 24613892
DOI: 10.1097/IIO.0000000000000017 -
International Journal of Medical... May 2021We investigated whether nanopore amplicon sequencing of aqueous humor was capable of rapid pathogen identification in infectious endophthalmitis.
OBJECTIVES
We investigated whether nanopore amplicon sequencing of aqueous humor was capable of rapid pathogen identification in infectious endophthalmitis.
METHODS
5 cases of culture-positive bacterial endophthalmitis and 3 cases of fungal endophthalmitis (1 culture-positive and 2 presumed) were included. DNA was extracted from the aqueous humor and vitreous specimen, and PCR of bacterial rDNA (16S) and fungal rDNA (ITS1 and D1/2/3) was performed. Then, nanopore amplicon sequencing was performed for 2 h. The results of amplicon sequencing were compared to those of conventional culture studies.
RESULTS
In all cases, pathogens were identified by amplicon sequencing of aqueous humor specimens. In 3 cases of bacterial endophthalmitis, the identified microbes were confirmed by culture studies of both aqueous humor and vitreous specimens. In 2 cases of bacterial and 1 case of fungal endophthalmitis, the identified pathogens were confirmed only by culture studies of vitreous specimens. In all cases, amplicon sequencing identified pathogen in a shorter turnaround time than culture studies. In 2 cases with negative culture results, amplicon sequencing of aqueous humor identified fungal pathogens.
CONCLUSIONS
Our data demonstrates the potential of amplicon nanopore sequencing using aqueous humor to enable rapid, sensitive and less invasive microbial diagnosis of endophthalmitis.
Topics: DNA, Bacterial; Endophthalmitis; Humans; Nanopore Sequencing; Nanopores; Vitreous Body
PubMed: 33930723
DOI: 10.1016/j.ijmm.2021.151505 -
Investigative Ophthalmology & Visual... Dec 2013Reduced quality of life and financial burden due to visual impairment and blindness begin to increase dramatically when individuals reach the age of 40. The major causes... (Review)
Review
Reduced quality of life and financial burden due to visual impairment and blindness begin to increase dramatically when individuals reach the age of 40. The major causes of age-related vision loss can be traced to changes to the structure and function of the lens, one of the tissues responsible for focusing light on the retina. Age-related nuclear cataracts, which are caused by aggregation and condensation of proteins, diminish vision because they impede the transmission and focusing of light on the retina. In addition to the slow-developing age-related form, cataracts often develop rapidly as a complication of ocular surgery, such as following vitrectomy or as a consequence of vitreous gel degeneration. Posterior capsular opacification, which can develop following cataract removal, is caused by proliferation and inappropriate accumulation of lens epithelial cells on the surfaces of intraocular lenses and the posterior lens capsule. Presbyopia is a loss of accommodative amplitude and reduced ability to shift focus from far to near objects. Onset of presbyopia is associated with an increase in lens hardness and reduced ability of the lens to change shape in response to ciliary muscle contraction. Avenues of promising research that seek to delay or prevent these causes of low vision are discussed in light of our current understanding of disease pathogenesis and some challenges that must be met to achieve success.
Topics: Aging; Disease Progression; Eye Diseases; Global Health; Humans; Lens, Crystalline; Prevalence; Vitreous Body
PubMed: 24335070
DOI: 10.1167/iovs.13-12940 -
Journal of Diabetes Research 2020To analyze the levels of B-cell-produced antibodies in the vitreous humor of patients with or without diabetic retinopathy (DR) both qualitatively and quantitatively.
AIM
To analyze the levels of B-cell-produced antibodies in the vitreous humor of patients with or without diabetic retinopathy (DR) both qualitatively and quantitatively.
METHODS
A total of 52 type 2 diabetes mellitus (T2DM) with DR patients and 52 control subjects without diabetes mellitus or inflammatory diseases were included in this prospective study. The levels of immunoglobulin (Ig)A, IgM, and IgG subtypes were measured using a magnetic color-bead-based multiplex assay.
RESULTS
The concentrations of IgA, IgM, and total antibodies in the DR group were significantly higher than those in the control group (all < 0.001), but there was no significant difference in the 4 IgG subtypes between the two groups after Bonferroni correction. Pearson's correlation analysis revealed low negative correlations between levels of antibodies (IgA, IgM) and estimated glomerular filtration rate (eGFR, = -0.443, = -0.377, respectively, both < 0.05). Furthermore, multiple linear regression analysis yielded three equations to predict the concentrations of IgA, IgM, and total antibodies in the vitreous humor according to eGFR and other clinical variables ( = 0.542, = 0.461, and = 0.312, respectively, all < 0.05).
CONCLUSION
Increased levels of IgA, IgM, and total antibodies produced by B cells were observed in the vitreous humor of T2DM patients with DR. There were low negative correlations between levels of antibodies (IgA, IgM) and eGFR.
Topics: Adult; Aged; B-Lymphocytes; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Male; Middle Aged; Vitreous Body
PubMed: 32714992
DOI: 10.1155/2020/4631290 -
Eye (London, England) May 2016Floaters are a common ocular condition which form as a consequence of aging changes in the vitreous. Although in most patients the symptoms are minimal, they can cause... (Review)
Review
Floaters are a common ocular condition which form as a consequence of aging changes in the vitreous. Although in most patients the symptoms are minimal, they can cause significant impairment in vision-related quality of life in a small population of patients. Recently there has been an increase in awareness of the visual disability caused by floaters, and the evidence-base for treatment of this condition using small-gauge vitrectomy has increased. In this review, we define the term 'floaters' as symptomatic vitreous opacities (SVO). We suggest a classification dependent on the presence or absence of posterior vitreous detachment and discuss their pathogenesis and natural history. We review their impact on patients' quality of life related to visual function. We review the psychological factors that may have a role in some patients who appear to be affected by SVO to the extent that they pursue all options including surgery with all its attendant risks. We summarise the available evidence-base of treatment options available for SVO with special emphasis on the safety and efficacy of vitrectomy for this condition.
Topics: Evidence-Based Medicine; Eye Diseases; Humans; Quality of Life; Vitrectomy; Vitreous Body
PubMed: 26939559
DOI: 10.1038/eye.2016.30