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Medicina (Kaunas, Lithuania) May 2024Primary open angle glaucoma (POAG) is defined as a "genetically complex trait", where modifying factors act on a genetic predisposing background. For the majority of... (Review)
Review
Primary open angle glaucoma (POAG) is defined as a "genetically complex trait", where modifying factors act on a genetic predisposing background. For the majority of glaucomatous conditions, DNA variants are not sufficient to explain pathogenesis. Some genes are clearly underlying the more "Mendelian" forms, while a growing number of related polymorphisms in other genes have been identified in recent years. Environmental, dietary, or biological factors are known to influence the development of the condition, but interactions between these factors and the genetic background are poorly understood. Several studies conducted in recent years have led to evidence that epigenetics, that is, changes in the pattern of gene expression without any changes in the DNA sequence, appear to be the missing link. Different epigenetic mechanisms have been proven to lead to glaucomatous changes in the eye, principally DNA methylation, post-translational histone modification, and RNA-associated gene regulation by non-coding RNAs. The aim of this work is to define the principal epigenetic actors in glaucoma pathogenesis. The identification of such mechanisms could potentially lead to new perspectives on therapeutic strategies.
Topics: Humans; Epigenesis, Genetic; DNA Methylation; Glaucoma, Open-Angle; Glaucoma; Genetic Predisposition to Disease
PubMed: 38929522
DOI: 10.3390/medicina60060905 -
Bioengineering (Basel, Switzerland) Jun 2024(1) Background: A rise in intraocular pressure (IOP) and decreased retinal ganglion cells are frequent indicators of effective modeling of chronic ocular hypertension in...
(1) Background: A rise in intraocular pressure (IOP) and decreased retinal ganglion cells are frequent indicators of effective modeling of chronic ocular hypertension in mice. In this study, the sensitivity of the mouse model to pharmaceutical therapy to reduce intraocular tension was assessed, the model's safety was confirmed using a cytotoxicity test, and the success rate of the mouse model of ocular hypertension was assessed by assessing alterations in IOP and neurons in the ganglion cell layer. (2) Methods: A mouse model of chronic ocular hypertension was produced in this study by employing photocrosslinkable sericin hydrogel injection and LED lamp irradiation. The eyes of 25 C57BL/6 male mice were subjected to 405 nm UV light from the front for 2 min after being injected with 5 μL of sericin hydrogel in the anterior chamber of the left eye. IOP in the mice was measured daily, and IOP rises greater than 5 mmHg were considered intraocular hypertension. When the IOP was lowered, the intervention was repeated once, but the interval between treatments was at least 2 weeks. The right eyes were not treated with anything as a normal control group. Mice eyeballs were stained with HE, Ni-type, and immunofluorescence to assess the model's efficacy. Two common drugs (tafluprost eye drops and timolol eye drops) were provided for one week after four weeks of stable IOP, and IOP changes were assessed to determine the drug sensitivity of the mouse model of chronic ocular hypertension. Furthermore, CellTiter 96 AQueous One Solution Cell Proliferation Assay (MTS) was utilized to investigate the safety of the ocular hypertension model by evaluating the deleterious effects of photocrosslinkable sericin hydrogel on cells. (3) Results: Before injection, the basal IOP was (9.42 ± 1.28) mmHg (1 kPa = 7.5 mmHg) in the experimental group and (9.08 ± 1.21) in the control group. After injection, cataract occurred in one eye, corneal edema in one eye, endophthalmitis in one eye, iris incarceration in one eye, and eyeball atrophy in one eye. Five mice with complications were excluded from the experiment, and twenty mice were left. Four weeks after injection, the IOP of the experimental group was maintained at (19.7 ± 4.52) mmHg, and that of the control group was maintained at (9.92 ± 1.55) mmHg, and the difference between the two groups was statistically significant ( < 0.05). Before the intervention, the IOP in the experimental group was (21.7 ± 3.31) mmHg in the high IOP control group, (20.33 ± 2.00) mmHg in the tafluprost eye drops group, and (20.67 ± 3.12) mmHg in the timolol maleate eye drops group. The IOP after the intervention was (23.2 ± 1.03) mmHg, (12.7 ± 2.11) mmHg, and (10.4 ± 1.43) mmHg, respectively. Before and after the intervention, there were no significant differences in the high-IOP control group ( > 0.05), there were statistically significant differences in the timolol eye drops group ( < 0.05), and there were statistically significant differences in the tafluprost eye drops group ( < 0.05). One week after drug withdrawal, there was no significant difference in IOP among the three groups ( > 0.05). In the high-IOP group, the protein (sericin hydrogel) showed a short strips or fragmented structure in the anterior chamber, accompanied by a large number of macrophages and a small number of plasma cells. The shape of the chamber angle was normal in the blank control group. The number of retinal ganglion cells decreased significantly 8 weeks after injection of sericin hydrogel into the anterior chamber, and the difference was statistically significant compared with the blank control group ( < 0.05). After the cells were treated with photocrosslinkable sericin hydrogel, there was no significant difference in the data of the CellTiter 96 assay kit of MTS compared with the blank control group ( > 0.05). (4) Conclusions: A mouse model of chronic intraocular hypertension can be established successfully by injecting sericin in the anterior chamber and irradiating with ultraviolet light. The model can simulate the structural and functional changes of glaucoma and can effectively reduce IOP after the action of most antihypertensive drugs, and it is highly sensitive to drugs. Sericin has no obvious toxic effect on cells and has high safety.
PubMed: 38927843
DOI: 10.3390/bioengineering11060607 -
Scientific Reports Jun 2024This study aims to assess the association between nicotine replacement therapy (NRT), varenicline, and untreated smoking with the risk of developing eye disorders. We...
This study aims to assess the association between nicotine replacement therapy (NRT), varenicline, and untreated smoking with the risk of developing eye disorders. We employed a new-user design to investigate the association between NRT use and the incidence of eye disorders by the Taiwan National Health Insurance program. This study included 8416 smokers who received NRT and 8416 smokers who did not receive NRT (control group) matched using propensity scores between 2007 and 2018. After adjustment for relevant factors, a multivariable Cox regression analysis revealed that compared with untreated smokers, NRT use was associated with a significantly reduced risk of macular degeneration (hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.13-0.87, P = 0.024). When stratified by dose, short-term NRT use (8-28 defined daily doses) was associated with significantly lower risk of glaucoma (HR: 0.35; 95% CI: 0.16-0.80, P = 0.012) and a trend toward reduced risk of cataract (HR: 0.60; 95% CI: 0.36-1.01, P = 0.053) compared to no treatment. However, these associations were not observed with long-term NRT use. The results of this real-world observational study indicate that NRT use, particularly short-term use, was associated with a lower risk of certain eye disorders compared to no treatment for smoking cessation. Long-term NRT use did not demonstrate the same benefits. Thus, short-term NRT may be a beneficial treatment strategy for reducing the risk of eye disorders in smokers attempting to quit. However, further evidence is required to verify these findings and determine the optimal duration of NRT use.
Topics: Humans; Male; Female; Smoking Cessation; Glaucoma; Middle Aged; Macular Degeneration; Retrospective Studies; Cataract; Taiwan; Aged; Adult; Smoking; Tobacco Use Cessation Devices; Incidence; Varenicline
PubMed: 38926484
DOI: 10.1038/s41598-024-65813-8 -
International Ophthalmology Jun 2024The aim of this study was to evaluate the lamina cribrosa curvature index in different types of glaucoma in comparison with clinical findings and conventional...
OBJECTIVE
The aim of this study was to evaluate the lamina cribrosa curvature index in different types of glaucoma in comparison with clinical findings and conventional measurement methods.
MATERIAL AND METHOD
Patients older than 18 years who were followed up in Glaucoma Unit of Department of Ophthalmology at Fırat University Faculty of Medicine, whose disease had been under control at least for 1 year, who had at least three reliable visual fields, whose refractive error was between - 6 and + 5 diopter and who did not have any disease other than glaucoma that would affect the visual field, were included in the study. Clinical and demographic characteristics, visual field, optical coherence tomography and lamina cribrosa curvature index (LCCI) results were evaluated. The study patients were divided into six groups: early-stage primary open-angle glaucoma (POAG) as group 1 and intermediate-advanced stage POAG as group 2, pseudo-exfoliation glaucoma (PEXG) as group 3, normal tension glaucoma (NTG) as group 4, ocular hypertension patients whom subsequently developed POAG as group 5 and healthy control as group 6.
RESULTS
A total of 189 eyes of 101 patients were included in our study. Forty-seven patients were male (46.5%) and 54 were female (53.5%). The mean age was 62.43 ± 1.49 years. LCCI, mean deviation (MD), visual field index (VFI), pattern standard deviation (PSD) and retinal nerve fiber layer thickness (RNFL) values were analyzed in all groups and Pearson correlation analysis showed statistically significant correlation between PSD and RNFL measurements with LCCI values in all groups. MD value was correlated with LCCI in groups 2, 3 and 4, while VFI value was correlated with LCCI in all groups except group 5. When the groups were compared with each other according to the Post-Hoc Tamhane test, LCCI measurement showed statistically significant results in accordance with MD, VFI, PSD and RNFL values.
CONCLUSION
The LCCI assessment is mostly consistent with conventional tests. In this study, in which different types of glaucoma and healthy subjects were examined simultaneously, LCCI shows promise as a detailed and reliable assessment method.
Topics: Humans; Male; Female; Tomography, Optical Coherence; Middle Aged; Visual Fields; Optic Disk; Intraocular Pressure; Aged; Glaucoma, Open-Angle; Retinal Ganglion Cells; Nerve Fibers; Adult; Follow-Up Studies; Glaucoma
PubMed: 38926206
DOI: 10.1007/s10792-024-03190-x -
Ceska a Slovenska Oftalmologie :... 2024Iridocorneal endothelial (ICE) syndrome is a rare disease characterized by abnormal proliferation and structural changes of the endothelium, obliteration of the...
AIM
Iridocorneal endothelial (ICE) syndrome is a rare disease characterized by abnormal proliferation and structural changes of the endothelium, obliteration of the iridocorneal angle, and anomalies of the iris. The consequence of these changes is secondary glaucoma and corneal decompensation. The etiology is unclear, and the syndrome more commonly affects middle-aged women.
CASE REPORTS
In this article we present two different case studies of young patients diagnosed with ICE syndrome with complications. The first case report is about a young woman in whom surgical treatment of glaucoma and corneal edema was successful. On the other hand, the second report presents a complicated case of a 29-year-old patient whose treatment was not successful despite repeated interventions.
CONCLUSION
This text highlights the complexity of ICE syndrome, the difficulty of its therapy and the importance of early diagnosis.
Topics: Humans; Female; Adult; Iridocorneal Endothelial Syndrome; Glaucoma
PubMed: 38925896
DOI: 10.31348/2024/27 -
Cornea Jun 2024To describe a novel technique in which a contact lens was used to facilitate Descemet membrane endothelial keratoplasty (DMEK) in an eye with an anterior chamber...
PURPOSE
To describe a novel technique in which a contact lens was used to facilitate Descemet membrane endothelial keratoplasty (DMEK) in an eye with an anterior chamber intraocular lens (ACIOL).
METHODS
A 71-year-old man with a long-standing ACIOL developed bullous keratopathy. As the patient was at high risk of complications due to multiple ocular comorbidities, DMEK was performed with the ACIOL left in the anterior chamber. An inserted cosmetic contact lens was used as a platform for the graft unfolding.
RESULTS
Partial graft detachment on the third postoperative day required rebubbling. This successfully cleared up the cornea after a few weeks. At the one-month follow-up, the uncorrected distance visual acuity improved to 20/50, with an endothelial cell loss of 35.2%. Steroid-induced ocular hypertension necessitated a trabeculectomy by the fifth postoperative month. At the sixth follow-up month, endothelial cell loss was 64%.
CONCLUSIONS
Contact lens-assisted DMEK is a safe procedure for eyes with an ACIOL. However, good foresight is needed regarding whether the ACIOL should be kept or exchanged.
PubMed: 38923507
DOI: 10.1097/ICO.0000000000003606 -
Advanced Science (Weinheim,... Jun 2024Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since...
Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma-derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV-miR-29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR-29s in RGC pathophysiology. It is showed that the overexpression of miR-29b-3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR-29b-3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV-miR-29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV-based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.
PubMed: 38923329
DOI: 10.1002/advs.202309307 -
International Ophthalmology Jun 2024To examine the rate of ciliary body detachment in patients with choroidal detachment following glaucoma surgery and its effect on the clinical course, management, and... (Observational Study)
Observational Study
PURPOSE
To examine the rate of ciliary body detachment in patients with choroidal detachment following glaucoma surgery and its effect on the clinical course, management, and prognosis.
METHODS
A prospective observational case-series study. Patients with choroidal detachment following glaucoma surgery in 2018-2019 were included. All underwent complete ophthalmological examination and ultrasound biomicroscopy for evaluation of the presence and extent of ciliary body detachment. Follow-up examinations including ultrasound biomicroscopy scans were performed at 1 week, 1 month, 3 months, and 6 months.
RESULTS
Eight patients (8 eyes) were enrolled, 4 male and 4 female, of mean age 72 years (range 60-83). Five patients underwent trabeculectomy with mitomycin C (0.02%), which was combined with phacoemulsification cataract extraction in one; two underwent Ahmed glaucoma valve implantations, and one underwent ab-interno Xen45 gel stent implantation with mitomycin C (0.02%). The mean intraocular pressure was 26.0 ± 7.65 mmHg preoperatively, dropping to 6.9 ± 2.64 mmHg on first postoperative day one. Mean time from surgery to diagnosis of choroidal detachment was 11.6 ± 5.73 days. Ciliary body detachment was identified by ultrasound biomicroscopy in all patients, ranging between one and four quadrants. All patients were treated with topical steroids and cycloplegics; three (37.5%) received oral steroids. No surgical intervention for the choroidal or ciliary body detachments was indicated.
CONCLUSIONS
In this real-world prospective study, concurrent ciliary body detachment was identified in all patients who presented with choroidal detachment following glaucoma surgery. This observation may deepen our understanding of the mechanism underlying the hypotony that is often seen after glaucoma surgery.
Topics: Humans; Male; Female; Ciliary Body; Aged; Prospective Studies; Middle Aged; Aged, 80 and over; Intraocular Pressure; Choroidal Effusions; Glaucoma; Postoperative Complications; Microscopy, Acoustic; Follow-Up Studies; Trabeculectomy; Glaucoma Drainage Implants; Visual Acuity; Uveal Diseases; Tomography, Optical Coherence
PubMed: 38922523
DOI: 10.1007/s10792-024-03219-1 -
Cells Jun 2024Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important...
Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGFβ affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-β1 and -β2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFβ-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.
Topics: Trabecular Meshwork; Humans; MicroRNAs; Glaucoma, Open-Angle; Transforming Growth Factor beta2; Transforming Growth Factor beta; Transforming Growth Factor beta1; Cells, Cultured; Gene Expression Regulation; Intraocular Pressure
PubMed: 38920689
DOI: 10.3390/cells13121060 -
Cells Jun 2024In the context of glaucoma, intraocular pressure (IOP) and age are recognized as the primary factors contributing to its onset and progression. However, significant...
In the context of glaucoma, intraocular pressure (IOP) and age are recognized as the primary factors contributing to its onset and progression. However, significant reductions in IOP fail to completely halt its advancement. An emerging body of literature highlights the role of neuroinflammation in glaucoma. This study aimed to explore Bromfenac's anti-inflammatory properties in mitigating neuroinflammation associated with glaucoma using an ischemia-reperfusion (IR) glaucoma model. Bromfenac's impact on microglia and astrocytes under pressure was assessed via Western blotting and an enzyme-linked immunosorbent assay. Immunohistochemical staining was used to evaluate glial activation and changes in inflammatory marker expression in the IR model. Bromfenac led to the downregulation of inflammatory markers, which were elevated in the conditions of elevated pressure, and necroptosis markers were downregulated in astrocytes. In the IR model, elevated levels of GFAP and Iba-1 indicated glial activation. Following Bromfenac administration, levels of iNOS, COX-2, and PGE2-R were reduced, suggesting a decrease in neuroinflammation. Furthermore, Bromfenac administration in the IR model resulted in the improved survival of retinal ganglion cells (RGCs) and preservation of retinal function, as demonstrated by immunohistochemical staining and electroretinography. In summary, Bromfenac proved effective in diminishing neuroinflammation and resulted in enhanced RGC survival.
Topics: Bromobenzenes; Animals; Benzophenones; Reperfusion Injury; Glaucoma; Disease Models, Animal; Astrocytes; Neuroinflammatory Diseases; Retinal Ganglion Cells; Microglia; Male; Intraocular Pressure; Rats
PubMed: 38920673
DOI: 10.3390/cells13121046