Pathogenesis Of Cataract Research Articles

The inflammatory potential of diet is associated with the risk of age-related eye diseases

Inflammation is involved in the pathogenesis of cataract, age-related macular degeneration (AMD), and possibly open-angle glaucoma (OAG). We assessed whether the inflammatory potential of diet (quantified using the dietary inflammatory index; DII) affects the incidence of these common blinding age-related eye diseases. Serum inflammation markers were investigated as possible mediators. Participants aged >45 years were selected from the prospective, population-based Rotterdam Study. From 1991 onwards, every 4-5 years, participants underwent extensive eye examinations. At baseline, blood samples and dietary data (using food frequency questionnaires) were collected. The DII was adapted based on the data available. Of the 7436 participants free of eye diseases at baseline, 4036 developed incident eye diseases during follow-up (cataract=2895, early-intermediate AMD=891, late AMD=81, OAG=169). The adapted DII (aDII) ranged from-4.26 (i.e., anti-inflammatory) to 4.53 (i.e., pro-inflammatory). A higher aDII was significantly associated with increased inflammation. A higher neutrophil-lymphocyte ratio (NLR) was associated with an increased risk of cataract and AMD. Additionally, complement component 3c (C3c) and systemic immune-inflammation index (SII) were associated with increased risks of cataract and late AMD, respectively. Every point increase in the aDII was associated with a 9% increased risk of cataract (Odds ratio [95% confidence interval]: 1.09 [1.04-1.14]). The NLR and C3c partly mediated this association. We also identified associations of the aDII with risk of AMD (early-intermediate AMD, OR [95% CI]: 1.11 [1.03-1.19]; late AMD, OR [95% CI]: 1.24 [1.02-1.53]). The NLR partly mediated these associations. The aDII was not associated with OAG. A pro-inflammatory diet was associated with increased risks of cataract and AMD. Particularly the NLR, a marker of subclinical inflammation, appears to be implicated. These findings are relevant for patients with AMD and substantiate the current recommendations to strive for a healthy lifestyle to prevent blindness.

Refolding Increases the Chaperone-like Activity of αH-Crystallin and Reduces Its Hydrodynamic Diameter to That of α-Crystallin.

αH-Crystallin, a high molecular weight form of α-crystallin, is one of the major proteins in the lens nucleus. This high molecular weight aggregate (HMWA) plays an important role in the pathogenesis of cataracts. We have shown that the chaperone-like activity of HMWA is 40% of that of α-crystallin from the lens cortex. Refolding with urea significantly increased-up to 260%-the chaperone-like activity of α-crystallin and slightly reduced its hydrodynamic diameter (Dh). HMWA refolding resulted in an increase in chaperone-like activity up to 120% and a significant reduction of Dh of protein particles compared with that of α-crystallin. It was shown that the chaperone-like activity of HMWA, α-crystallin, and refolded α-crystallin but not refolded HMWA was strongly correlated with the denaturation enthalpy measured with differential scanning calorimetry (DSC). The DSC data demonstrated a significant increase in the native protein portion of refolded α-crystallin in comparison with authentic α-crystallin; however, the denaturation enthalpy of refolded HMWA was significantly decreased in comparison with authentic HMWA. The authors suggested that the increase in the chaperone-like activity of both α-crystallin and HMWA could be the result of the correction of misfolded proteins during renaturation and the rearrangement of protein supramolecular structures.

The human lens is capable of trilineage differentiation towards osteo-, chondro-, and adipogenesis-a model for studying cataract pathogenesis.

The potential for trilineage differentiation of cells in tissues represents a model for studying disease pathogenesis and regeneration pathways. Human lens trilineage differentiation has not yet been demonstrated, and so has calcification and osteogenic differentiation of human lens epithelial cells in the whole human lens. Such changes can pose a risk for complications during cataract surgery. Human lens capsules (n = 9) from cataract patients undergoing uneventful surgery were trilineage-differentiated toward osteogenesis, chondrogenesis, and adipogenesis. Furthermore, whole human healthy lenses (n = 3) collected from cadaveric eyes were differentiated into bone and characterized by immunohistochemistry. The cells in the human lens capsules were capable of undergoing trilineage differentiation, while the whole human healthy lenses could undergo osteogenesis differentiation, expressing osteocalcin, collagen I, and pigment epithelium-derived factor. We, hereby, show an ex vivo model for cataract formation through different stages of opacification, as well as provide in vivo evidence from patients undergoing calcified lens extraction with bone-like consistency.

Identification of the Most Impactful Asparagine Residues for γS-Crystallin Aggregation by Deamidation.

Crystallin aggregation in the eye lens is involved in the pathogenesis of cataracts. The aggregation is considered to be promoted by non-enzymatic post-translational modifications, such as the deamidation and stereoinversion of amino acid residues. Although in a previous study, the deamidated asparagine residues were detected in γS-crystallin in vivo, it is unclear which deamidated residues have the most impact on the aggregation under physiological conditions. In this study, we investigated the deamidation impacts of all Asn residues in γS-crystallin for the structural and aggregation properties utilizing deamidation mimetic mutants (N14D, N37D, N53D, N76D, and N143D). The structural impacts were investigated using circular dichroism analysis and molecular dynamics simulations, and the aggregation properties were analyzed by gel filtration chromatography and spectrophotometric methods. No significant structural impacts of all mutations were detected. However, the N37D mutation decreased thermal stability and changed some intermolecular hydrogen-bond formations. Aggregation analysis indicated that the superiority of the aggregation rate in each mutant varied with temperature. Deamidation at any Asn residues promoted γS-crystallin aggregation, and the deamidation at Asn37, Asn53, and Asn76 were suggested to be the most impactful in the formation of insoluble aggregations.

ԿԱՏԱՐԱԿՏԻ ՈՒԼՏՐԱՁԱՅՆԱՅԻՆ ՖԱԿՈԷՄՈՒԼՍԻՖԻԿԱՑԻԱՅԻ ԱՐԴՅՈՒՆԱՎԵՏՈՒԹՅԱՆ ԽՆԴԻՐՆԵՐԻ ՎԵՐԱԲԵՐՅԱԼ

Cataract is a common disease, which occupies a leading position in the world among the causes of blindness. The interaction of many factors plays a role in the pathogenesis of cataract. Treatment of cataracts is only surgical. Ultrasonic phacoemulsification is the leading method for restoring vision in cataracts. It is recognized worldwide as the most effective and safest method for restoring vision in cataracts. The way of ultrasonic phacoemulsification is widespread all over the world - up to 95% of cases of cataract surgeries in Russia, Western Europe, and the United States are carried out using this technique. One of the main tendencies in modern cataract phacoemulsification is an increase in the efficiency of the use of ultrasonic energy. Further development of the cataract treatment technique is the search of ways to reduce surgical trauma and the invasiveness of intervention on the lens, which is due to the fact that ultrasonic destruction of the lens is combined with a negative effect, in particular, on the endothelium or posterior epithelium of the cornea, which can seriously affect the outcome of the operation itself. The high density of the lens nucleus with a combination of low density of corneal endothelial cells substantially complicates the task of the surgeon. During life, the density of endothelial cells decreases. Even non-complicated operations for cataracts lead to their loss up to 12-20%. Recovery of endothelial cells occurs due to their migration and hypertrophy. Based on the foregoing, there is a need to develop a criterion that can be used to predict the effectiveness of ultrasonic phacoemulsification in terms of the preservation of corneal endothelial cells. The morphofunctional state of the endothelial cells of the cornea and the cornea itself can become such criterion: the area and thickness of the cornea, the number of endothelial cells and their ratio. We are convinced that it is the morphofunctional state of the endothelial cells of the cornea and the cornea itself that should become the basis for an accurate estimate of the ultrasound energy.

LncRNA TUG1 regulates Smac/DIABLO expression by competitively inhibiting miR-29b and modulates the apoptosis of lens epithelial cells in age-related cataracts.

As one of the early discovered long non-coding RNAs (lncRNA), taurine upregulation gene 1 (TUG1) has been widely expressed in a variety of tumors. Moreover, it promotes cell proliferation, differentiation, apoptosis, and migration. However, our understanding of its importance in the pathogenesis of cataracts remains limited. This study aimed to explore the mechanism by which lncRNA TUG1 mediates lens epithelial cell apoptosis in age-related cataracts (ARC) by regulating the microRNAs (miR-29b)/second mitochondria-derived activator of caspases axis, and to identify more non-surgical strategies for cataract treatment. The messenger RNA expression levels of TUG1, miR-29b, and Smac were detected using quantitative real-time polymerase chain reaction in vivo and in vitro. The expression of the Smac protein was analyzed by Western blotting and immunofluorescence. Flow cytometry and cell counting kit-8 assays were used to detect the cell apoptosis and proliferation rates, respectively. The targeted regulatory relationship between lncRNA TUG1, miR-29b, and Smac was verified by viral vector construction, co-transfection, nuclear and cytoplasmic separation, luciferase reporter assays, and RNA immunoprecipitation. TUG1 and Smac were expressed at high levels in ARC and HLE-B3 cells treated with 200 μmol/L H2O2, whereas miR-29b expression was decreased. In vitro cell experiments confirmed that down-regulation of TUG1 could inhibit the apoptosis of lens epithelial cells. Mechanistically, Smac expression was negatively regulated by miR-29b. TUG1 competitively inhibited miR-29b expression and caused greater release of Smac. In addition, miR-29b partially reversed the effects of TUG1 on human lens epithelial cell line cells. lncRNA TUG1 increases Smac expression and promotes apoptosis of lens epithelial cells in ARC by competitively inhibiting miR-29b. This mechanism is the cytological basis for ARC formation. Based on these results, the lncRNA TUG1/miR29b/Smac axis may be a new molecular pathway that regulates ARC development.

Ubiquitination of Ku70 by Parkin promotes apoptosis of lens epithelial cells.

Oxidative damage-triggered apoptosis in lens epithelial cells is considered as a main risk factor in the pathogenesis of age-related cataracts. Ku70 is a key factor in the DNA repair process of double-strand breaks. In the present study, we aimed to investigate the role of Ku70 and its related E3 ubiquitin ligase in lens epithelial cell apoptosis. The levels of Ku70 in the anterior lens capsules of human cataracts and Emory mice were lower compared to controls. H2 O2 treatment resulted in decreased expression of Ku70 through accelerating Ku70 ubiquitination. Parkin, an E3 ubiquitin ligase, could interact with Ku70 and promote the ubiquitination and degradation of this protein. In addition, ubiquitinated Ku70 was regulated by ubiquitin-proteasome, autophagy-lysosome and mitophagy pathways. Ectopic expression of Ku70 protected SRA01/04 cells from H2 O2 -induced apoptosis, whereas silencing Ku70 exhibited the opposite trend. Co-transfected with Parkin non-ubiquitinatable Ku70 mutant could maintain its anti-apoptosis ability, whereas wild-type Ku70 failed. Moreover, Ku70 might facilitate mitochondrial fusion by increasing the expression of Mitofusin 1/2. The present study revealed that Parkin-mediated Ku70 ubiquitination facilitated H2 O2 -induced lens epithelial cell apoptosis through alleviating mitochondrial fusion, which could provide potential targets for age-related cataract treatment.

Current Approach to the Pathogenesis of Diabetic Cataracts.

Cataracts remain the first or second leading cause of blindness in all world regions. In the diabetic population, cataracts not only have a 3-5 times higher incidence than in the healthy population but also affect people at a younger age. In patients with type 1 diabetes, cataracts occur on average 20 years earlier than in the non-diabetic population. In addition, the risk of developing cataracts increases with the duration of diabetes and poor metabolic control. A better understanding of the mechanisms leading to the formation of diabetic cataracts enables more effective treatment and a holistic approach to the patient.

CeRNA network construction and identification of hub genes as novel therapeutic targets for age-related cataracts using bioinformatics.

The aim of this study is to investigate the genetic and epigenetic mechanisms involved in the pathogenesis of age-related cataract (ARC). We obtained the transcriptome datafile of th ree ARC samples and three healthy, age-matched samples and used differential expression analyses to identify the differentially expressed genes (DEGs). The differential lncRNA-associated competing endogenous (ceRNA) network, and the protein-protein network (PPI) were constructed using Cytoscape and STRING. Cluster analyses were performed to identify the underlying molecular mechanisms of the hub genes affecting ARC progression. To verify the immune status of the ARC patients, immune-associated analyses were also conducted. The PPI network identified the FOXO1 gene as the hub gene with the highest score, as calculated by the Maximal Clique Centrality (MCC) algorithm. The ceRNA network identified lncRNAs H19, XIST, TTTY14, and MEG3 and hub genes FOXO1, NOTCH3, CDK6, SPRY2, and CA2 as playing key roles in regulating the pathogenesis of ARC. Additionally, the identified hub genes showed no significant correlation with an immune response but were highly correlated with cell metabolism, including cysteine, methionine, and galactose. The findings of this study may provide clues toward ARC pathogenic mechanisms and may be of significance for future therapeutic research.

DNA DAMAGE IN LENS EPITHELIAL CELLS OF SENILE CATARACT PATIENTS OF DIFFERENT PRAKRITI ACCORDING TO AYURVEDA LITERATURE

Objectives: The Ayurvedic concept of the constitution is useful in predicting an individual’s susceptibility to age-related diseases like Cataracts (Kaphaja Linganasha). The objectives of the study were to assess DNA damage directly in human lens epithelial cells (HLEC) of senile cataracts of Vata Predominant, Pitta Predominant, and Kapha Predominant Prakriti individuals. Methods: After obtaining Institutional Ethics Committee permission, HLEC were taken from 20 Vatta Predominant,20 Pitta Predominant and 20 Kapha Predominant Prakriti individuals of cataract after cataract surgery and from 4 controls in which quantitative assessment of DNA damage were measured using CometScore™ software. The formation of “comets” in the DNA of lens epithelial cells can be visualized through the method of single gel electrophoresis and indicates DNA strand breaks, as the damaged DNA migrates at a different rate than non-damaged DNA during electrophoresis. Results: No such prominent comets were indicating any DNA damage in the HLEC of the four control subjects, but comets were found in cataractous HLEC. The maximal damage was found in pitta-predominant Prakriti Individuals. In senile cataract patients, in HLECs DNA was randomly damaged and this type of damage was possible by reactive oxygen species. The DNA damage in HLEC was found maximally in pitta Predominant Prakriti individuals of senile type of cataract patients. Statistical significance was observed between senile cataracts in pitta predominant Prakriti versus senile cataracts in Vata predominant Prakriti individuals and between senile cataracts in Vata predominant Prakriti versus senile cataracts in Kapha Prakriti individual. No statistically significant results were obtained for senile cataracts in pitta Prakriti versus senile cataracts in Kapha Prakriti individuals. Conclusion: The pathogenesis of senile cataracts is multifactorial and includes continuous molecular stress brought by photo-oxidative stress, UV irradiation, and oxidative reactions.

Age-related cataract: GSTP1 ubiquitination and degradation by Parkin inhibits its anti-apoptosis in lens epithelial cells

PurposeOxidative stress-induced apoptosis of lens epithelial cells (LECs) contributes to the pathogenesis of age-related cataract (ARC). The purpose of this research is to underlie the potential mechanism of E3 ligase Parkin and its oxidative stress-associated substrate in cataractogenesis. MethodsThe central anterior capsules were obtained from patients with ARC, Emory mice, and corresponding controls. SRA01/04 cells were exposed to H2O2 combined with cycloheximide (a translational inhibitor), MG-132 (a proteasome inhibitor), chloroquine (an autophagy inhibitor), Mdivi-1 (a mitochondrial division inhibitor), respectively. Co-immunoprecipitation was employed to detect protein-protein interactions and ubiquitin-tagged protein products. Levels of proteins and mRNA were evaluated by western blotting and quantitative RT-PCR assays. ResultsGlutathione-S-transferase P1 (GSTP1) was identified as a novel Parkin substrate. Compared with corresponding controls, GSTP1 was significantly decreased in the anterior lens capsules obtained from human cataracts and Emory mice. Similarly, GSTP1 was declined in H2O2-stimulated SRA01/04 cells. Ectopic expression of GSTP1 mitigated H2O2-induced apoptosis, whereas silencing GSTP1 aggregated apoptosis. In addition, H2O2 stimulation and Parkin overexpression could promote the degradation of GSTP1 through the ubiquitin-proteasome system, autophagy-lysosome pathway, and mitophagy. After co-transfection with Parkin, the non-ubiquitinatable GSTP1 mutant maintained its anti-apoptotic function, while wildtype GSTP1 failed. Mechanistically, GSTP1 might promote mitochondrial fusion through upregulating Mitofusins 1/2 (MFN1/2). ConclusionOxidative stress induces LECs apoptosis via Parkin-regulated degradation of GSTP1, which may provide potential targets for ARC therapy.

In vitro assessment of the severity of deoxyribonucleic acid damage in different types of cataracts directly in lens epithelial cells.

This study aimed to assess the severity of deoxyribonucleic acid (DNA) damage in lens epithelial cells (LECs) of senile cortical, nuclear, and posterior subcapsular cataracts. LECs were obtained from senile cortical, nuclear, and subcapsular types of cataracts after surgery. DNA damage in the cells was immediately assessed quantitatively using the CometScore™ software. Comets were found in cataractous LECs. The formation of "comets" in the DNA of LECs can be visualized using single-cell gel electrophoresis and indicates DNA strand breaks because the damaged DNA migrates at a different rate than the nondamaged DNA. Maximal damage was observed in Grade 3 cortical, nuclear, and subcapsular forms of cataracts. Statistically significant DNA damage was seen between grades 1 and 3 of cortical type of cataract, grades 1 and 3 of nuclear type of cataract, and grades 2 and 3 and grades 1 and 3 of posterior subcapsular type of cataract. In patients with senile cataract, DNA of LECs was randomly damaged, and this type of damage was possibly caused by reactive oxygen species (ROS). Maximum DNA damage was found in patients with Grade 3 senile cortical, nuclear, and subcapsular type cataracts. The pathogenesis of senile cataracts is multifactorial and includes continuous molecular stress resulting from photooxidative stress, UV irradiation, and oxidative reactions.

Изменения хрусталика при осложненной миопии. Возможности лечения

Cataracts are the leading cause of vision loss in patients over 50 years. In addition to senile cataracts, its earlier development due to various risk factors (for example, degenerative myopia characterized by lens opacity even in low myopia) is also an issue. This article discusses the pathogenesis of cataracts with a focus on oxidative stress, which is also important for myopia progression. The published and authors' data on the association between myopia and cataracts are addressed. The importance of early diagnosis of cataract in patients with myopia at the stage of lens suture compaction and its early radial and meridional opacities (that is possible with maximum mydriasis) is emphasized. Potential complex therapy with anti-cataract drops characterized by antioxidant effect is discussed as a pathogenetic approach to delay cataract progression in patients who (for various reasons) are not suitable for surgery. Recommendations for modifying the lifestyle to prevent cataract development are provided. KEYWORDS: degenerative myopia, myopic cataract, lens, oxidative stress, antioxidants, risk factors, drug treatment, pirenoxine. FOR CITATION: Rabadanova M.G., Oganezova J.G., Kremkova E.V., Yakh'yaeva M.M. Lens disorders in degenerative myopia. Treatment options. Russian Journal of Clinical Ophthalmology. 2023;23(4):207–212 (in Russ.). DOI: 10.32364/2311-7729-2023-23-4-6.

Integrative Bioinformatics Analysis of mRNA Expression Profiles of Mice to Explore the Key Genes Involved in Crim1 Mutation-Induced Congenital Cataracts

Crim1 has been implicated in cataracts in mice and is of great importance in the development of the eye in both humans and mice. Therefore, we aimed to clarify how Crim1 mutations affect lens development and the molecular mechanism of cataracts in mice through comprehensive bioinformatics analysis. The microarray chip was downloaded from the GEO database to obtain the gene expression profile data set. Differentially expressed genes (DEGs) were screened using the limma package. GO and KEGG analyses of DEGs were performed using the DAVID database. Then, we established the protein–protein interaction (PPI) network in Cytoscape. Next, we used MCODE to analyze the data. We obtained 750 DEGs in total, including 407 upregulated DEGs and 343 downregulated DEGs. GO analysis showed that the DEGs were mainly related to biological processes, such as apoptosis, cell translation and the immune system. KEGG analysis showed that the enriched functions and pathways were related to the processing and presentation of ribosomes, lysosomes, and antigens. We identified 18 HUB genes, among which four core genes, C1qa, C1qb, C1qc, and Cd74, were closely related to congenital cataracts induced by Crim1 mutation. This study reveals the molecular pathogenesis of congenital cataracts induced by Crim1, and this information is expected to facilitate clinical genetic testing, molecular diagnosis, prognosis, and individualized chemotherapy for congenital cataracts (CC).

In Vitro Inhibitory Activity and Molecular Docking Study of Selected Natural Phenolic Compounds as AR and SDH Inhibitors**

AbstractPolyol pathway enzymes, aldose reductase (EC 1.1.1.21; AR, ALR2), and sorbitol dehydrogenase (EC 1.1.1.14; SDH, SORD) have been widely investigated as the enzymes crucially involved in the pathogenesis of several chronic complications, including nephropathy, neuropathy, retinopathy, and cataracts associated with diabetes mellitus. Although phenolic compounds have been reported to possess many other biological activities, in continuation of our interest in designing and discovering potent inhibitors of AR and SDH, herein, we have evaluated these agents’ inhibitory potential against polyol pathway enzymes. Our in vitro studies revealed that all the derivatives show activity against recombinant human AR (rhAR) and SDH (rhSDH), with KI constants ranging from 9.37±0.16 μM to 77.22±2.49 μM and 2.51±0.10 μM to 42.16±1.03 μM, respectively. Among these agents, Prunetin and Phloridzin showed prominent inhibitory activity versus rhAR and rhSDH, while some were also determined to possess perfect dual activity. Moreover, in silico studies were also performed to rationalize binding site interactions of these agents with the target enzyme AR and SDH. According to ADME‐Tox was also determined that these derivatives be agents exhibiting suitable drug‐like properties. The compounds identified therapeutic potentials in this study may be promising for developing lead therapeutic agents to prevent polyol pathway complications.

Extraction and Purification of Flavonoids from Buddleja officinalis Maxim and Their Attenuation of H2O2-Induced Cell Injury by Modulating Oxidative Stress and Autophagy.

Cataracts are an ailment representing the leading cause of blindness in the world. The pathogenesis of cataracts is not clear, and there is no effective treatment. An increasing amount of evidence shows that oxidative stress and autophagy in lens epithelial cells play a key role in the occurrence and development of cataracts. Buddleja officinalis Maxim flavonoids (BMF) are natural antioxidants and regulators that present anti-inflammatory and anti-tumor effects, among others. In this study, we optimized the extraction method of BMFs and detected three of their main active monomers (luteolin, apigenin, and acacetin). In addition, a model of oxidative damage model using rabbit lens epithelial cells induced by hydrogen peroxide (H2O2). By detecting the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), and OH (OH), the expression of autophagosomes and autolysosomes were observed after MRFP-GFP-LC3 adenovirus was introduced into the cells. Western blotting was used to detect the expression of Beclin-1 and P62. Our research results showed that the optimal extraction parameters to obtain the highest yield of total flavonoids were a liquid−solid ratio of 1:31 g/mL, an ethanol volume fraction of 67%, an extraction time of 2.6 h, and an extraction temperature of 58 °C. Moreover, the content of luteolin was 690.85 ppb, that of apigenin was 114.91 ppb, and the content of acacetin was 5.617 ppb. After oxidative damage was induced by H2O2, the cell survival rate decreased significantly. BMFs could increase the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decrease the levels of malondialdehyde (MDA) and OH (OH). After the MRFP-GFP-LC3 virus was introduced into rabbit lens epithelial cells and detecting the expression of P62 and Beclin-1, we found that the intervention of BMF could promote the binding of autophagosomes to lysosomes. Compared with the model group, the level of P62 in the low-, middle-, and high-dose groups of BMF was significantly down-regulated, the level of Beclin-1 was significantly increased, and the difference was statistically significant (p < 0.05). In other words, the optimized extraction method was better than others, and the purified BMF contained three main active monomers (luteolin, apigenin, and acacetin). In addition, BMFs could ameliorate the H2O2-induced oxidative damage to rabbit lens cells by promoting autophagy and regulating the level of antioxidation.

Advances in pathogenesis and pharmacotherapy of cataract

<p indent="0mm">Cataract is the leading cause of vision impairment worldwide. As the population ages, the prevalence of cataract will increase rapidly, which has caused a substantial social and economic burden. Although cataract surgery is effective, it still suffers from complications and high costs and could not meet the increasing surgery demand. Therefore, pharmacological treatment for cataracts is cheaper and more readily available for patients. Therefore, research on the pathogenesis of cataract and exploring potential therapeutic drugs for cataract have always been a research hotspot for years. Based on our team’s current work, this article summarizes the pathogenesis and pharmacotherapy strategies of cataract from the pathogenesis of cataract, the cataract disease models, and the development of anti-cataract drugs.

Changes in the Lipid Profile of Aqueous Humor From Diabetic Cataract Patients.

To identify the differential profiles of lipids in aqueous humor (AH) between control and diabetic cataract patients. The lipidomic profiles of 19 samples from patients with diabetic cataract (diabetic group) and 32 controls (control group) were analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS). Differentially expressed lipids between the two groups were determined through partial least-squares-discriminant analysis and principal component analysis. Receiver operating characteristic curve was calculated to evaluate the diagnostic value of differentially expressed lipids in distinguishing diabetic cataract patients from the control subjects. The correlations of the target lipids with the serum lipids were determined by Pearson correlation. The results of LC-MS/MS analysis revealed a remarkable variation in lipid class composition. As compared with the control group, the percentage of triglycerides (TGs) was higher and that of Ceramide-1-phosphates was significantly lower in the AH of the diabetic group. A multivariate analysis of the lipid species showed that the expression levels of 16 of 639 lipids significantly changed in the diabetic group as compared to the control group. Among them, TG (42:6) (area under curve [AUC] = 0.985, P < 0.0001) and diacylglycerol (DG) (24:2) (AUC = 0.944, P < 0.0001) exhibited high prediction capability for diabetic cataract. The results of Pearson correlation revealed that the concentrations of TG (42:6) in AH were positively correlated with serum TG levels in diabetic patients. The lipid composition of AH of diabetic cataract patients showed a significant difference from that of the healthy subjects. Lipid changes, especially the high AH levels of TG (42:6) and DG (24:2), might contribute to cataractogenesis and possibly be involved in the development of diabetic cataract. Changes in the lipid profile of AH may partly account for the pathogenesis of diabetic cataracts and lead to a novel therapeutic strategy for diabetic cataract.

Ectopic circSTK39 Expression Ameliorates Hydrogen Peroxide-Induced Human Lens Epithelial Cell Apoptosis and Oxidative Stress through the miR-125a-5p/ERCC6 Pathway

PurposeMore and more studies suggest that circular RNA (circRNA) is involved in the pathogenesis of age-related cataract (ARC). CircSTK39, a circular RNA, has inhibitory effects on cancer progression. However, there is no data regarding the role of circSTK39 in ARC occurrence and the underlying mechanism.MethodsARC cell model was established by inducing lens epithelial cells (SRA01/04) using hydrogen peroxide (H2O2). CircSTK39, microRNA-125a-5p (miR-125a-5p), and ERCC excision repair 6, chromatin remodeling factor (ERCC6) expression were detected by quantitative real-time polymerase chain reaction. Western blot was conducted to assess protein expression. Cell viability, proliferation, and apoptosis were investigated by cell counting kit-8 assay, 5-Ethynyl-29-deoxyuridine assay, and flow cytometry analysis, respectively. Oxidative stress was evaluated using commercial kits. Dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay were used to identify the relationship between miR-125a-5p and circSTK39 or ERCC6.ResultsCircSTK39 and ERCC6 expression were significantly downregulated, but miR-125a-5p expression was upregulated in the lens tissues of ARC patients and H2O2-treated SRA01/04 cells. H2O2 treatment led to decreased cell proliferation and increased cell apoptosis and oxidative stress, accompanied by the increases of C-caspase3 and Bax expression and the decrease of Bcl-2 expression; however, these effects were reversed after circSTK39 overexpression. MiR-125a-5p was found to participate in H2O2-triggered cell damage by interacting with circSTK39. Additionally, ERCC6 silencing inhibited circSTK39 overexpression-mediated action. Importantly, circSTK39 regulated ERCC6 expression by interaction with miR-125a-5p in H2O2-treated SRA01/04 cells.ConclusionThe increased expression of circSTK39 ameliorated H2O2-induced SRA01/04 cell injury through the miR-125a-5p/ERCC6 pathway.

LBODP084 Bilateral Cataracts In A 15-year-old Girl With New-onset Type 1 Diabetes Mellitus

Abstract Background Cataracts secondary to Type 1 or Type 2 Diabetes is not uncommon in adults, however, it is a rare finding in pediatrics patients with Type 1 Diabetes. Clinical Case A 15-year-old girl presented with progressively worsened bilateral vision for 6 months, however, vision rapidly deteriorated over the previous month, prompting visit to optometrist. No history of weight loss, however, did report 1.5 years of polydipsia, polyuria, and polyphagia. Outside optometrist reported concerns for cataracts. She presented to our Ophthalmology department one week later, who found bilateral cataracts with haziness in all layers and swollen lenses. Labs were done due to findings, glucose was 668 mg/dL with HbA1C &amp;gt;20%. She presented next day to ER, reported no symptoms other than blurry vision but was found to be in mild DKA with a venous pH of 7.285, Ketones 5.41 mmol/L, Glucose 480 mg/dL, and C-peptide 0.32 pmol/mL. Patient was started on insulin infusion at 0.1u/kg/hour and transitioned quickly to subcutaneous insulin. Pancreatic antibodies were significant for positive GAD65 and ZnT8 antibodies. She had cataract surgery for her left eye 1 week after presentation, found to have intumescent white cataract with "hand motion" vision. Vision in left eye is now 20/20 with plans to operate on the right eye in the near future. Literature Review: The prevalence of early diabetic cataracts in the pediatric population can range from 0.7%- 3.4% (1); and more common in female patients (2). Pathophysiology includes defect in the polyol pathway, combined with oxidative stress, leading to increased fluid retention (3). Treatment involves cataract surgery and improved glycemic control. Current ISPAD guidelines recommend initial evaluation for cataracts, and subsequent surveillance concomitant with diabetic retinopathy monitoring biennially with those with good glycemic control (4). Conclusion Diabetic cataracts are extremely rare in the pediatric population. However, diabetes should be considered as an etiology for juvenile cataracts. Given the rapid formation and severity of onset of bilateral cataracts for this patient, early and frequent ophthalmologic surveillance should be recommended for Type 1 diabetes pediatric population. Reference: 1. Šimunović, M, et al (2018). Cataract as early ocular complication in children and adolescents with type 1 diabetes mellitus. International Journal of Endocrinology, 2018, 1–6. 2. Lu, W. -L, et al (2020). High risk of early cataracts in young type 1 diabetes group: A nationwide cohort study. International Journal of Endocrinology, 2020, 1–8. 3. Pollreisz, A, et al (2010). Diabetic cataract pathogenesis, epidemiology and treatment. Journal of Ophthalmology, 2010, 1–8. 4. Donaghue, KC, et al (2018). ISPAD Clinical Practice Consensus Guidelines 2018: Microvascular and macrovascular complications in children and adolescents. Pediatric Diabetes, 19, 262–274. Presentation: No date and time listed