Pathophysiology Of Cataract Research Articles

Differential Signaling Pathways Identified in Aqueous Humor, Anterior Capsule, and Crystalline Lens of Age-Related, Diabetic, and Post-Vitrectomy Cataract

Background: The purpose of this study was to detect proteomic alterations and corresponding signaling pathways involved in the formation of age-related cataract (ARC), diabetic cataract (DC), and post-vitrectomy cataract (PVC). Methods: Three sample types, the aqueous humor (AH), the anterior capsule (AC), and the content of the phaco cassette, were collected during phacoemulsification surgery. The samples were obtained from 12 participants without diabetes mellitus (DM), 11 participants with DM, and 7 participants without DM, with a history of vitrectomy surgery in the past 12 months. The Sp3 protocol (Single-Pot, Solid-Phase, Sample-Preparation) was used for the sample preparation. The recognition and quantification of proteins were carried out with liquid chromatography online with tandem mass spectrometry. The DIA-NN software was applied for the identification and quantification of peptides/proteins. Statistical analysis and data visualization were conducted on Perseus software. Data are available via ProteomeXchange. Results: A very rich atlas of the lens and AH proteome has been generated. Glycosaminoglycan biosynthesis and the non-canonical Wnt receptor signaling pathway were differentially expressed in ARC compared to both the DC and PVC groups. In the PVC group, complement activation was differentially expressed in AH samples, while glutathione metabolism and oxidoreductase activity were differentially expressed in AC samples. Microfilament motor activity, microtubule cytoskeleton organization, and microtubule binding were differentially expressed in the DC and PVC groups in both AH and AC samples. Conclusions: The results of this study expand the existing knowledge on pathways involved in the pathophysiology of cataract, and suggest possible important druggable targets for slower progression or even prevention of cataract.

Are lipid-lowering drugs associated with a risk of cataract? A pharmacovigilance study.

Some reports have raised concerns regarding a potential risk of cataracts associated with statins. However, clinical and observational studies evaluating the risk led to conflicting results. We assessed whether lipid-lowering drugs (LLD) use is associated with an increased risk of cataract using the WHO's Individual Case Safety Reports database, VigiBase® . We performed a disproportionality analysis with all reports between 1/1/1988 and 12/31/2018 to measure the reporting risk of 'cataract' in patients ≥45years. Primary analysis compared LLD users to non-users. To mitigate some potential confounding bias, we performed several sensitivity analyses excluding reports (i) with an association of at least two LLD, (ii) with antidiabetic and glucocorticoids and (iii) with lovastatin. We also analyzed the data according to the different classes of age limiting the period of study to years 2002-2012. We identified 14664 reports of cataract (3049 in LLD users, 66% women, 66±20years). Statins (84%, atorvastatin, simvastatin, rosuvastatin and lovastatin) were mostly reported, followed by fibrates (5.7%), nicotinic acid (3%), bile acid sequestrants (2%), herbal cholesterol and triglyceride reducers (2%) and others (ezetimibe, PCSK9 inhibitors, 15%). LLD users were associated with a greater risk of reports than non-users (ROR 2.47, 95% CI 2.37-2.57). This association was also found for statins in general, fibrates, bile sequestrants, nicotinic acid, herbal drugs and others. Similar trends were observed in sensitivity analyses (except for fibrates and nicotinic acid after exclusion of reports with at least two LLD or in older patients ≥75years). Using a large real-life database (>18.5 million reports), we found a signal of cataract for LLD as a whole and statins, bile sequestrants and herbal drugs in particular. The signal disappeared for fibrates and nicotinic acid in older patients. No definite conclusions can be made for ezetimibe or PCSK9 inhibitors (evolocumab and alirocumab). This suggests that a decrease in cholesterol could be important in the pathophysiology of cataract in patients exposed to the main LLD.

Pathophysiology of cataracts

Cataracts result in significant vision reduction. It is estimated that cataract was responsible for the morbidity of 10.8 million people (of overall 32.4 million blind people around the world), and 35.1 million people (of overall 191 million vision impaired people around the world). It is also the most common cause of blindness in many countries, including Saudi Arabia. We tried to understand, in details, the pathogenesis of cataracts, with special focus on how ageing is a contributory factor in its development. We conducted this review using a comprehensive search of MEDLINE, PubMed and EMBASE from January 1970 to March 2017. The following search terms were used: cataracts, pathogenesis of cataracts, pathophysiology in cataracts, ageing lens, aging and vision loss, lens degeneration. Cataracts heavily impacts the vision, thereby, the lives of individuals suffering from it. Due to its large prevalence, the impact on economy is large too. Although surgery is very promising, newer approach is focusing on its pathophysiology to emphasize on preventive options. Several changes, including oxidative stress, reduction in reductive enzymes, lens elasticity, and specific age related degeneration play major roles in its pathophysiology.

Evaluation of programmed cell death processes on the lens epithelium of older dogs with diabetic and hypermature cataracts

It is well known that posterior capsule opacification (PCO), one of the most common late postoperative complications of cataract surgery, is mainly caused by proliferation and differentiation of remaining lens epithelial cells (LECs) on the posterior lens capsule. Many authors suggest that alterations induced by the pathophysiology of cataracts, its metabolism and the use of 0.1% trypan blue (TB) must cause some degree of cellular damage on these cells, wicht would help to prevent and/or reduce the incidence of PCO after cataract surgery in humans. Therefore, the aim of this study was to evaluate the expression of cell death markers on LECs of older dogs with diabetic and hypermature cataracts, after capsulorhexis, both using 0.1% TB. Twenty samples collected from 13 dogs of different breeds, with ages varying from 8 to 12 years-old, with diabetic and hypermature cataracts, which had been subjected to phacoemulsification surgery (Phaco) using 0.1% TB for staining were studied. Animals were classified as dogs with diabetic (DC) and hypermature cataracts (HC), and expression of molecular markers for apoptosis and autophagy (caspase-3 and beclin-1) on LECs were obtained by immunofluorescence technique. The expression of caspase-3 and beclin-1 was observed in every studied sample and did not differ between groups. In conclusion, our findings suggest that apoptosis and autophagy processes occur to LECs in older dogs presenting diabetic and hypermature cataracts after Phaco utilizing 0.1% TB. Our results may be helpful to future studies of PCO in post-phacoemulsification surgery patients.

Cataracts Pathophysiology and Managements

Background: Cataract is defined as the loss of lens transparency because of opacification of the lens. Age-related cataract is the most prevalent type in adults, with the onset between age 45 to 50 years, while in children hereditary and metabolic causes are most common. Aim of the work: In this study, our aim was to discuss the epidemiology, pathophysiology, classification, risk factors, symptoms, and management of cataracts. Methodology: Weconducted this review using a comprehensive search of MEDLINE, PubMed and EMBASE from January 1981 to March 2017. The following search terms were used: cataracts, causes of cataract, pathophysiology of cataract, management of cataract. Conclusion: Cataract is one of the most common causes of blindness worldwide, and more prevalent in developing countries. It is also the most curable cause of blindness which involves a simple surgical procedure.

The Pathophysiology of Cataract and Major Interventions to Retarding Its Progression: A Mini Review

Cataracts are the principal cause of blindness globally affecting the older cohort specifically those in their fifth decades and beyond In fact there are more cases of cataracts worldwide than there are of glaucoma macular degeneration and diabetic retinopathy DR combined according to Prevent Blindness America PBA Whilst ageing remains the predominant risk factor for cataract formation other predisposing factors such as diabetes mellitus DM nutritional and trace element deficiency ultraviolet radiations smoking etc have been implicated in this sight threatening condition The pathophysiology of cataract is not fully understood albeit aldose reductase inhibitors and antioxidants have proven beneficial in the prevention and management of this vision threatening condition in vitro and in vivo experimental studies This paper seeks to provide an overview of the understanding of the pathophysiology of cataract and the major interventions that have been deployed to help retard its progression as highlighted in extant literature

The role of melatonin as an antioxidant in human lens epithelial cells

Oxidative stress plays a significant role in pathophysiology of cataracts and also known to affect the phosphatidylinositol-3-kinase/ protein kinase B (PI3K/Akt) signaling pathway. This well-documented pathway is involved in protecting against apoptosis-inducing insults, including oxidative stress. Melatonin (N-acetyl-5-methoxy-tryptamine), the major secretory product of the pineal gland, was identified as a powerful free radical scavenger and a broad-spectrum antioxidant that defends against various oxidative stress-associated diseases. This study was conducted to determine whether melatonin could prevent hydrogen peroxide (H2O2)-induced oxidative stress in human lens epithelial cells (HLECs) and to elucidate the molecular pathways involved in this protection. HLECs were subjected to various concentrations of H2O2 in the presence or absence of melatonin at different concentrations. Cell viability was monitored by a 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl-tetrazoliumbromide (MTT) assay, and the apoptosis rate and intracellular reactive oxygen species (ROS) levels were measured by flow cytometry using annexin V-FITC and propidium iodide (PI) staining. The expression levels of HO-1, Nrf-2, CAT, and MDA were measured using Western blot analysis. Akt activation was also evaluated by Western blot analysis. The data from our study showed that cells pretreated with melatonin can reduce H2O2-induced intracellular ROS generation and thus protect HLECs from cell apoptosis. Furthermore, we found that melatonin is a potent activator of Akt in HLECs. Our findings suggest that in addition to functioning as a direct free radical scavenger, melatonin can elicit cellular signaling pathways that are protective against oxidative stress-induced cataracts.

The Potential Role of Dietary Xanthophylls in Cataract and Age-Related Macular Degeneration

The carotenoid xanthophylls, lutein and zeaxanthin, accumulate in the eye lens and macular region of the retina. Lutein and zeaxanthin concentrations in the macula are greater than those found in plasma and other tissues. A relationship between macular pigment optical density, a marker of lutein and zeaxanthin concentration in the macula, and lens optical density, an antecedent of cataractous changes, has been suggested. The xanthophylls may act to protect the eye from ultraviolet phototoxicity via quenching reactive oxygen species and/or other mechanisms. Some observational studies have shown that generous intakes of lutein and zeaxanthin, particularly from certain xanthophyll-rich foods like spinach, broccoli and eggs, are associated with a significant reduction in the risk for cataract (up to 20%) and for age-related macular degeneration (up to 40%). While the pathophysiology of cataract and age-related macular degeneration is complex and contains both environmental and genetic components, research studies suggest dietary factors including antioxidant vitamins and xanthophylls may contribute to a reduction in the risk of these degenerative eye diseases. Further research is necessary to confirm these observations.

Pathophysiology of cataracts: Copper ion and peroxidation in diabetics

The concentration of copper ion in cataractous lenses was higher than that in clear lenses. The concentration of copper ion was significantly higher in subjects with diabetes (DM group) than in subjects without diabetes (control group). The concentration of Cu2+ ion was significantly greater than that of Cu+ ion in the DM group. Furthermore, the concentration of copper ion unconjugated to protein was higher than that of protein-conjugated copper ion. It is assumed that in the cataractous lenses of the DM group, a decrease in the reactivity of the copper-containing enzyme superoxide dismutase and an increase in hydrogen peroxide concentration leads to the generation of hydroxyl radicals from the Fenton's-type reaction. In diabetes, an increase in lenticular glucose induces glycation with the release of copper ion from copper-containing enzymes, thus increasing the concentration of lenticular copper ion. As a result, superoxide scavenging activity is reduced and peroxide lipid concentration is increased. This is assumed to result from the hyperactivity of the peroxidation cascade.

Pathophysiology of cataract

Pathophysiology of cataract

Pathophysiology of cataract

Pathophysiology of cataract

Pathogenesis and pathophysiology of cataracts

Pathogenesis and pathophysiology of cataracts