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1.
FASEB J ; 38(14): e23832, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39046354

RESUMO

This study aims to investigate the hypothesis that Yes-associated protein (YAP) significantly regulates antioxidant potential and anti-apoptosis in UVB-induced cataract by exploring the underlying molecular mechanisms. To investigate the association between YAP and cataract, various experimental techniques were employed, including cell viability assessment, Annexin V FITC/PI assay, measurement of ROS production, RT-PCR, Western blot assay, and Immunoprecipitation. UVB exposure on human lens epithelium cells (HLECs) reduced total and nuclear YAP protein expression, increased cleaved/pro-caspase 3 ratios, decreased cell viability, and elevated ROS levels compared to controls. Similar Western blot results were observed in in vivo experiments involving UVB-treated mice. YAP knockdown in vitro demonstrated a decrease in the protein expression of FOXM1, Nrf2, and HO-1, which correlated with the mRNA expression, accompanied by an increase in cell apoptosis, caspase 3 activation, and the release of ROS. Conversely, YAP overexpression mitigated these effects induced by UVB irradiation. Immunoprecipitation revealed a FOXM1-YAP interaction. Notably, inhibiting FOXM1 decreased Nrf2 and HO-1, activating caspase 3. Additionally, administering the ROS inhibitor N-acetyl-L-cysteine (NAC) effectively mitigated the apoptotic effects induced by oxidative stress from UVB irradiation, rescuing the protein expression levels of YAP, FOXM1, Nrf2, and HO-1. The initial findings of our study demonstrate the existence of a feedback loop involving YAP, FOXM1, Nrf2, and ROS that significantly influences the cell apoptosis in HLECs under UVB-induced oxidative stress.


Assuntos
Apoptose , Catarata , Proteína Forkhead Box M1 , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Raios Ultravioleta , Proteínas de Sinalização YAP , Apoptose/efeitos da radiação , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Raios Ultravioleta/efeitos adversos , Humanos , Animais , Proteína Forkhead Box M1/metabolismo , Proteína Forkhead Box M1/genética , Camundongos , Catarata/etiologia , Catarata/metabolismo , Catarata/patologia , Proteínas de Sinalização YAP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Cristalino/metabolismo , Cristalino/efeitos da radiação , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Espécies Reativas de Oxigênio/metabolismo , Masculino , Transdução de Sinais , Camundongos Endogâmicos C57BL
2.
FASEB J ; 38(17): e23861, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39247969

RESUMO

Recently, amyloid-ß oligomers (AßOs) have been studied as the primary pathogenic substances in Alzheimer's disease (AD). Our previous study revealed that the Aß expression level is closely related to ARC progression. Here, we demonstrated that the accumulation of AßOs in the lens epithelium of age-related cataract (ARC) patients increased during ARC progression and that this alteration was consistent with the changes in mitochondrial function, oxidative stress, and cellular apoptosis. In vitro, human lens epithelial cells (HLECs) treated with AßOs exhibited Ca2+ dyshomeostasis, impaired mitochondrial function, elevated oxidative stress levels, and increased apoptosis. Moreover, the proapoptotic effect of AßOs was alleviated after the uptake of mitochondrial Ca2+ was inhibited. These results establish that AßOs may promote HLEC apoptosis by inducing mitochondrial Ca2+ overload, thus preliminarily revealing the possible association between the accumulation of AßOs and other pathological processes in ARC.


Assuntos
Peptídeos beta-Amiloides , Apoptose , Catarata , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Envelhecimento/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Cálcio/metabolismo , Catarata/metabolismo , Catarata/patologia , Células Cultivadas , Células Epiteliais/metabolismo , Cristalino/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo
3.
J Cell Physiol ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38828927

RESUMO

Age-related cataract (ARC) is regarded as the principal cause of vision impairment among the aged. The regulatory role of long noncoding RNAs (LncRNAs) in ARC remains unclear. The lncRNA maternally expressed gene 3 (MEG3) has been reported to promote ARC progression, and the underlying mechanism was further investigated in this study. Lens epithelium samples were collected to verify the expression of MEG3. Lens epithelial cells (LECs) were treated with H2O2 to mimic microenvironment of ARC in vitro. Cell viability, reactive oxygen species, and ferroptosis were evaluated during the in viro experiments. In the present work, lncRNA MEG3 was highly expressed in ARC group, compared with normal group. MEG3 was induced, cell viability and glutathione peroxidase 4 (GPX4) level were inhibited, and ferroptosis was promoted in H2O2 treated LECs. LncRNA MEG3 silence reversed the effects of H2O2 on viability and ferroptosis in LECs. Thereafter, lncRNA MEG3 was found to bind to PTBP1 for GPX4 degradation. Silencing of GPX4 reversed the regulation of lncRNA MEG3 inhibition in H2O2-treated LECs. To sum up, lncRNA MEG3 exhibited high expression in ARC. In H2O2-induced LECs, inhibition of lncRNA MEG3 accelerated cell viability and repressed ferroptosis by interaction with PTBP1 for GPX4 messenger RNA decay. Targeting lncRNA MEG3 may be a novel treatment of ARC.

4.
Exp Eye Res ; 241: 109817, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38340945

RESUMO

Previous studies have shown that the development of age-related cataract (ARC) is involved in lens epithelium dysfunction, which is associated with abnormally expressed circular RNAs (circRNAs). The current work aims to probe the role of circSTRBP (hsa_circ_0088,427) in hydrogen peroxide (H2O2)-induced lens epitheliums. Lens epithelium tissues were harvested from ARC or normal subjects (n = 23). CircSTRBP, spermatid perinuclear RNA binding protein (STRBP), and nicotinamide adenine dinucleotide phosphate oxidase subunit 4 (NOX4) levels were measured using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell proliferation, cycle progression, and apoptosis were assessed using 5-ethynyl-2'-deoxyuridine (EdU), Cell Counting Kit-8 (CCK-8), and flow cytometry assays. Caspase 3 activity, reactive oxygen species (ROS), malondialdehyde (MDA), and Glutathione peroxidases (GSH-PX) levels were detected using corresponding kits. NOX4 protein level was determined using Western blot. The interaction between insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and circSTRBP or NOX4 was assessed through RNA immunoprecipitation (RIP). CircSTRBP and NOX4 abundances were increased in lens epithelium samples from ARC patients and H2O2-treated SRA01/04 cells. CircSTRBP knockdown might abolish H2O2-triggered SRA01/04 cell proliferation repression and apoptosis and oxidative stress promotion. In mechanism, circSTRBP is bound with IGF2BP1 and improves the stability and expression of NOX4 mRNA in SRA01/04 cells. CircSTRBP facilitated H2O2-induced SRA01/04 cell apoptosis and oxidative stress through by enhancing NOX4 mRNA stability via recruiting IGF2BP1, providing novel insights for ARC progression and treatment.


Assuntos
Catarata , Cristalino , MicroRNAs , Humanos , Peróxido de Hidrogênio/toxicidade , Peróxido de Hidrogênio/metabolismo , Estresse Oxidativo , Cristalino/metabolismo , Apoptose , Catarata/genética , Catarata/metabolismo , Epitélio/metabolismo , NADPH Oxidase 4/genética , NADPH Oxidase 4/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , MicroRNAs/genética
5.
Int Ophthalmol ; 44(1): 232, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861013

RESUMO

PURPOSE: To explore the application effect of cervical pillow in phacoemulsification surgery for age-related cataract patients. METHODS: 104 cases of age-related cataract patients admitted to our hospital in June 2023 were enrolled and divided into the control group (traditional supine position) and the experimental group (the cervical pillow supine position) by the digital parity method (52 cases per group). The two groups were evaluated for the discomfort score, the satisfaction of patients and doctors, the head displacement rate, the number of displacement, the operation time and the time of body position during the operation and after the operation. RESULTS: There was no significant difference in the gender (P = 0.84), age (P = 0.86), course of disease (P = 0.82) and the time spent on position placement (P = 0.15) of the two groups. The patient in the experimental group had lower discomfort score (P = 0.0001), higher patients satisfaction (P = 0.0001) and higher doctors satisfaction (P = 0.0001) than patients in the control group. There was no significant difference between the experimental group and the control group in the proportion of intraoperative (P = 0.36) and postoperative pain (P = 0.65). Besides, the number of head transfers (P = 0.001), number of head shifts (P = 0.0001), the surgical time (P = 0.0001) and laparoscopic time (P = 0.0001) in the experimental group were significantly lower than those in the control group. CONCLUSION: The additional cervical pillow for age-related cataract patients in the traditional supine position during the operation will not increase the preparation time before the operation, but will help improve the patient satisfaction, improve the comfort and maintain a good position of the operative eye field, bringing obvious comfort and smooth operation for the surgeon in the operation, thus reducing the risk of the operation, shortening the operation time.


Assuntos
Facoemulsificação , Humanos , Feminino , Masculino , Facoemulsificação/métodos , Estudos Prospectivos , Idoso , Pessoa de Meia-Idade , Satisfação do Paciente , Catarata/complicações , Acuidade Visual , Duração da Cirurgia
6.
Int Ophthalmol ; 44(1): 142, 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38493427

RESUMO

PURPOSE: The purpose of this study was to investigate the effect of circ_HLCS on age-related cataract (ARC). METHODS: Circ_HLCS, microRNA (miR)-338-3p, and bisphosphate 3'-nucleotidase 1 (BPNT1) were quantified by quantitative real-time polymerase chain reaction or western blot. Cell proliferation and cell viability were assessed by the 5-Ethynyl-2'-deoxyuridinr and cell counting kit-8 assays. Cell apoptosis was detected by flow cytometry. Targeted correlations among circ_HLCS, miR-338-3p, and BPNT1 were verified by the dual-luciferase reporter and RNA pull-down assays. RESULTS: circ_HLCS was diminished in ARC tissues and UV-treated SRA01/04 cells. Elevated content of circ_HLCS undermined UV-induced cell proliferation inhibition and apoptosis. Mechanistically, circ_HLCS directly targeted miR-338-3p, and circ_HLCS regulated BPNT1 expression through miR-338-3p. Furthermore, reduction of miR-338-3p ameliorated UV-induced SRA01/04 cell damage by increasing BPNT1 expression. CONCLUSION: Taken together, these data suggested that circ_HLCS inhibited apoptosis of UV-treated SRA01/04 cells by miR-338-3p/BPNT1 axis. Therefore, circ_HLCS might be a potential therapeutic target for ARC.


Assuntos
Cristalino , MicroRNAs , Humanos , RNA Circular/genética , Apoptose , Proliferação de Células , Células Epiteliais , MicroRNAs/genética
7.
Int Ophthalmol ; 44(1): 288, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937308

RESUMO

PURPOSE: Age-related cataract (ARC) is the most common cause of visual impairment and blindness in older adults. However, the role of CUL4B in the ARC remains unclear. Therefore, we investigated CUL4B expression and its effects on apoptosis. MATERIALS AND METHODS: CUL4B expression levels were detected by a quantitative real-time polymerase chain reaction from the anterior lens capsules of patients with ARC and HLE-B3 cells treated with different concentrations of H2O2. CUL4B expression was silenced by siRNA transfection to evaluate apoptosis. CUL4B and apoptotic proteins B cell lymphoma 2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), caspase-3, cleaved caspase-3, Bax, Bak, and Bid were assessed using western blot analysis. Apoptosis was monitored using the TUNEL assay. RESULTS: CUL4B expression was downregulated in the anterior lens capsules (P < 0.0001) and H2O2-treated HLE-B3 cells (P = 0.0405). CUL4B protein levels were significantly lower in 100 µmol/L (P = 0.0012) and 200 µmol/L (P = 0.0041) H2O2-treated HLE-B3 cells than in the untreated cells. CUL4B expression was significantly knocked down at the mRNA (P = 0.0043) and protein levels (P = 0.0002) in HLE-B3 cells. Bcl-2 (P = 0.0199), Mcl-1 (P = 0.0042), and caspase-3 (P = 0.0142) were significantly downregulated, whereas cleaved caspase-3 (P = 0.0089) and Bak (P = 0.009) were significantly upregulated in the knockdown group. The TUNEL assay showed a greater induction of apoptosis. CONCLUSIONS: CUL4B downregulation promotes the apoptosis of lens epithelial cells. Our study may help in understanding the role of CUL4B in ARC pathogenesis.


Assuntos
Apoptose , Catarata , Proteínas Culina , Humanos , Catarata/metabolismo , Catarata/genética , Catarata/etiologia , Proteínas Culina/genética , Proteínas Culina/metabolismo , Proteínas Culina/biossíntese , Masculino , Feminino , Idoso , Western Blotting , Reação em Cadeia da Polimerase em Tempo Real , Pessoa de Meia-Idade , Envelhecimento , Regulação da Expressão Gênica , Cápsula do Cristalino/metabolismo , Cápsula do Cristalino/patologia , Marcação In Situ das Extremidades Cortadas
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(4): 553-561, 2024 Apr 28.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-39019784

RESUMO

OBJECTIVES: Age-related cataract is the most common type of adult cataract and a leading cause of blindness. Currently, there are few reports on the establishment of animal models for age-related cataract. During the experimental breeding of Microtus fortis (M. fortis), we first observed that M. fortis aged 12 to 15 months could naturally develop cataracts. This study aims to explore the possibility of developing them as an animal model for age-related cataract via identifing and analyzing spontaneous cataract in M. fortis. METHODS: The 12-month-old healthy M. fortis were served as a control group and 12-month-old cataractous M. fortis were served as an experimental group. The lens transparency was observed using the slit-lamp biomicroscope. Hematoxylin and eosin staining was used to detect pathological changes in the lens. Biochemical detection methods were applied to detect blood routine, blood glucose levels, the serum activities of superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in both groups. Finally, real-time RT-PCR was used to detect the transcription levels of cataract-related genes in the lens of 2 groups. RESULTS: Compared with the control group, the lens of cataract M. fortis showed severely visible opacity, the structure of lens was destroyed seriously, and some pathological damage, such as swelling, degeneration/necrosis, calcification, hyperplasia, and fiber liquefaction were found in lens epithelial cells (LECs). The fibrous structure was disorganized and irregularly distributed with morgagnian globules (MGs) aggregated in the degenerated lens fibers. There was no statistically significant difference in blood glucose levels between the experimental and control groups (P>0.05). However, white blood cell (WBC) count (P<0.05), lymphocyte count (P<0.01), and lymphocyte ratio (P<0.05) were significantly decreased, while neutrophil percentage (P<0.05) and monocyte ratio (P<0.01) were significantly increased. The serum activities of SOD and GSH-Px (both P<0.05) were both reduced. The mRNAs of cataract-related genes, including CRYAA, CRYBA1, CRYBB3, Bsfp1, GJA3, CRYBA2, MIP, HspB1, DNase2B, and GJA8, were significantly downregultaed in the lenses of the experimental group (all P<0.05). CONCLUSIONS: There are significant differences in lens pathological changes, peroxidase levels, and cataract-related gene expression between cataract and healthy M. fortis. The developed cataract spontaneously in M. fortis is closely related to age, the cataract M. fortis might be an ideal animal model for the research of age-related cataract.


Assuntos
Arvicolinae , Catarata , Glutationa Peroxidase , Cristalino , Superóxido Dismutase , Animais , Catarata/genética , Catarata/patologia , Catarata/etiologia , Cristalino/patologia , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Glutationa Peroxidase/sangue , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Envelhecimento , Modelos Animais de Doenças
9.
J Biol Chem ; 298(11): 102537, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36174677

RESUMO

In the human eye, a transparent cornea and lens combine to form the "refracton" to focus images on the retina. This requires the refracton to have a high refractive index "n," mediated largely by extracellular collagen fibrils in the corneal stroma and the highly concentrated crystallin proteins in the cytoplasm of the lens fiber cells. Transparency is a result of short-range order in the spatial arrangement of corneal collagen fibrils and lens crystallins, generated in part by post-translational modifications (PTMs). However, while corneal collagen is remodeled continuously and replaced, lens crystallins are very long-lived and are not replaced and so accumulate PTMs over a lifetime. Eventually, a tipping point is reached when protein aggregation results in increased light scatter, inevitably leading to the iconic protein condensation-based disease, age-related cataract (ARC). Cataracts account for 50% of vision impairment worldwide, affecting far more people than other well-known protein aggregation-based diseases. However, because accumulation of crystallin PTMs begins before birth and long before ARC presents, we postulate that the lens protein PTMs contribute to a "cataractogenic load" that not only increases with age but also has protective effects on optical function by stabilizing lens crystallins until a tipping point is reached. In this review, we highlight decades of experimental findings that support the potential for PTMs to be protective during normal development. We hypothesize that ARC is preventable by protecting the biochemical and biophysical properties of lens proteins needed to maintain transparency, refraction, and optical function.


Assuntos
Catarata , Cristalinas , Cristalino , Humanos , Catarata/metabolismo , Cristalinas/metabolismo , Cristalino/metabolismo , Agregados Proteicos , Colágeno/metabolismo , Envelhecimento
10.
BMC Ophthalmol ; 23(1): 267, 2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37312173

RESUMO

BACKGROUND: Persistent hyperplastic primary vitreous (PHPV), also known as persistent fetal vasculature (PFV), is a clinical entity that traditionally presents with leukocoria, microphthalmia, retinal dysplasia, or eyeball shrinkage which is associated with poor vision. However, there is a dearth of literature on cases of PHPV in adulthood or with asymptomatic occurrence. This report presents the clinical and pathological findings of a non-typical PHPV case and discuss the current knowledge for this condition. CASE PRESENTATION: A 68-year-old healthy male was referred to our outpatient department for evaluation of age-related cataract without other visual symptoms. Preoperative fundus examination occasionally detected an isolated stalk-like band extending to the posterior pole of the eye with normal central vitreous and retina. Other ocular examinations including b-mode ultrasonography, optical coherence tomography did not unveil any abnormalities, which caused diagnostic uncertainty. We referred to cataract surgery along with histopathological study, that revealed characteristics of PHPV including fibrous connective tissues mainly composed of fibrocyte proliferation and a very few capillary vessels. Thereafter, a definitive diagnosis of non-typical PHPV was established. CONCLUSION: Our case is unique due to it was not discovered until adulthood, presence with only age-related cataract, and accompanied with normal central vitreous and retina. Histopathological explorations lead to an accurate diagnosis of the condition. Those results broaden the phenotype spectrums of PHPV and further provide clinical clues for the cognition of the disease.


Assuntos
Extração de Catarata , Catarata , Vítreo Primário Hiperplásico Persistente , Humanos , Masculino , Catarata/diagnóstico , Fundo de Olho , Vítreo Primário Hiperplásico Persistente/diagnóstico , Retina , Idoso
11.
BMC Ophthalmol ; 23(1): 192, 2023 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-37131205

RESUMO

BACKGROUND: Cataract is commonly observed in patients with primary angle-closure glaucoma; however, its underlying pathological mechanisms remain unclear. This study aimed to improve our knowledge on the pathological processes involved in primary angle-closure glaucoma (PACG) by identifying potential prognostic genes associated with cataract progression. METHODS: Thirty anterior capsular membrane samples were collected from PACG patients with cataracts and age-related cataracts. Differentially expressed genes (DEGs) between these two cohorts were analyzed using high-throughput sequencing. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to screen the DEGs, and potential prognostic markers and their coexpression network were then predicted by bioinformatic analyses. The DEGs were further validated by reverse transcription-quantitative polymerase chain reaction. RESULTS: A total of 399 DEGs were found to be specifically associated with cataracts development in PACG patients, among which 177 and 221 DEGs were upregulated and downregulated, respectively. STRING and Cytoscape network analyses revealed seven genes-CTGF, FOS, CAV1, CYR61, ICAM1, EGR1, and NR4A1-that were remarkably enriched and mainly involved in the MAPK, PI3K/Akt, Toll-like receptor, and TNF signaling pathways. RT-qPCR-based validation further confirmed that the sequencing results were accurate and reliable. CONCLUSIONS: Herein, we identified seven genes and their signaling pathways that may contribute to cataract progression in patients with high intraocular pressure. Taken together, our findings highlight new molecular mechanisms that may explain the high incidence of cataracts in PACG patients. In addition, the genes identified herein may represent new foundations for the development of therapeutic strategies for PACG with cataract.


Assuntos
Catarata , Glaucoma de Ângulo Fechado , Humanos , RNA-Seq , Glaucoma de Ângulo Fechado/genética , Glaucoma de Ângulo Fechado/metabolismo , Fosfatidilinositol 3-Quinases , Catarata/genética , Prognóstico
12.
BMC Ophthalmol ; 23(1): 514, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110879

RESUMO

BACKGROUND: In the present study, we explored the role of N6-methyladenosine (m6A) modification of long non-coding RNAs (lncRNAs) and its association with ferroptosis in lens epithelium cells (LECs) of age-related cataract (ARC). METHODS: Through m6A RNA immunoprecipitation sequencing (m6A-RIP-seq) and RNA sequencing (RNA-seq), we identified m6A mediated and differentially expressed lncRNAs (dme-lncRNAs) in ARC patients. Based on bioinformatics analysis, we selected critical dme-lncRNAs and pathways associated with ARC formation to reveal their potential molecular mechanisms. The downregulation of glutathione peroxidase 4 (GPX4), a key component of ferroptosis, was confirmed by real-time RT-PCR (RT-qPCR) and Western blotting in age-related cortical cataract (ARCC) samples. Transmission electron microscopy was used to assess the change in mitochondrial in LECs. RESULTS: The analysis revealed a total of 11,193 m6A peaks within lncRNAs, among which 7043 were enriched and 4150 were depleted. Among those, lncRNA ENST00000586817(upstream of the GPX4 gene) was not only significantly upregulated in the LECs of ARCC but also potentially augmented the expression of GPX4 through a cis mechanism. The expression of m6A-modified lncRNA (ENST00000586817) was correlated with that of GPX4 and was downregulated in ARC patients. The TEM results indicated significant mitochondrial changes in ARCC samples. GPX4 downregulation enhanced LEC ferroptosis and decreased viability via RSL3 in SRA01/04 cells. CONCLUSIONS: Our results provide insight into the potential function of m6A-modified lncRNAs. M6A-modified lncRNA ENST00000586817 might regulate the expression of GPX4 by a cis mechanism and be implicated in ferroptosis in ARCs.


Assuntos
Catarata , Ferroptose , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , RNA Longo não Codificante , Humanos , Catarata/genética , Catarata/metabolismo , Epitélio/metabolismo , Ferroptose/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , RNA Longo não Codificante/genética
13.
BMC Ophthalmol ; 23(1): 480, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993828

RESUMO

BACKGROUND: The spatial position of the lens in patients with cortical age-related cataract (CARC) is unclear. We investigated a basis for the assessment of visual quality after cataract surgery by analysing the ultrasound biomicroscopic characteristics of the biological parameters of the lens in patients with CARC. METHODS: In this retrospective study, 119 patients (50 males and 69 females, totalling 238 eyes) with CARC who underwent simple cataract surgery were selected. The lens thickness (LT), axial length (AL), anterior chamber depth (ACD), lens vault (LV), trabecular-iris angle (TIA), iris-lens angle (ILA), iris-lens contact distance (ILCD) were measured by A-scan ultrasound and ultrasound biomicroscopy. The corresponding lens position (LP) and relative lens position (RLP) were calculated. RESULTS: LP was greater in men than in women (P < 0.05), LV was smaller in men than in women (P = 0.002), ILA and ILCD were not statistically significant (P = 0.072 and P = 0.854, respectively). There were significant differences in TIA, ILA, and ILCD in the four quadrants (all P < 0.05), with a trend in the distribution of TIA: superior < inferior < nasal < temporal, ILA: nasal < inferior < temporal < superior, and ILCD: superior < temporal < inferior < nasal. CONCLUSIONS: The lens protrudes more obviously in females than in males and the lens tilts to a certain extent with the increase of age and tends to be more upward and temporal in the supine position. Therefore, trends in lens-related parameters in patients with CARC should be taken seriously.


Assuntos
Catarata , Glaucoma de Ângulo Fechado , Cristalino , Masculino , Humanos , Feminino , Microscopia Acústica , Estudos Retrospectivos , Cristalino/diagnóstico por imagem , Câmara Anterior/diagnóstico por imagem , Iris/diagnóstico por imagem
14.
Biochem Genet ; 61(2): 565-577, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36002666

RESUMO

Age-related cataract (ARC) is one of the most common chronic diseases. Circular RNA (circ)_HIPK3 is reported to be involved in the advancement of ARC, but its molecular mechanism has not been clarified. Our study provides a new perspective on the clinical treatment of ARC. Our data showed that the expression levels of circ_HIPK3 and histone deacetylase 4 (HDAC4) were downregulated, while microRNA (miR)-495-3p level was increased in ARC tissues and H2O2-induced SRA01/04 cells. Functional experiments showed that circ_HIPK3 and HDAC4 overexpression could inhibit H2O2-induced lens epithelial cell apoptosis and fibrosis. In terms of mechanism, we found that circ_HIPK3 could sponge miR-495-3p, miR-495-3p could target HDAC4. Besides, we confirmed that circ_HIPK3 sponged miR-495-3p to positively regulate HDAC4. Additionally, miR-495-3p overexpression or HDAC4 knockdown reversed the inhibition effect of circ_HIPK3 on H2O2-induced lens epithelial cell injury. In conclusion, our data showed that circ_HIPK3 suppressed H2O2-induced lens epithelial cell injury by regulating miR-495-3p/HDAC4 axis.


Assuntos
Catarata , MicroRNAs , Humanos , Peróxido de Hidrogênio/farmacologia , Células Epiteliais , Apoptose , Histona Desacetilases/genética , RNA Circular/genética , Catarata/genética , MicroRNAs/genética , Proliferação de Células , Proteínas Serina-Treonina Quinases , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas Repressoras/genética
15.
J Clin Biochem Nutr ; 72(1): 54-60, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36777073

RESUMO

We comprehensively assessed the roles of systemic redox markers by including both prooxidant and antioxidant markers in 121 Japanese subjects (mean ±â€…SD age, 70 ±â€…11 years; 38 men) with no ocular pathology except age-related cataract. Serum levels of lipid peroxides, ferric-reducing activity, and thiol antioxidant activity were measured using the diacron reactive oxygen metabolite (dROM), biologic antioxidant potential (BAP), and sulfhydryl (SH) tests, respectively, using a free-radical analyzer. Univariate analyses suggested that older age, higher pulse rate, worse best-corrected visual acuity (BCVA), higher intraocular pressure, and higher cataract grade were associated with a lower SH level. Scatterplots revealed virtually linear associations between age and the SH level (estimate, -4.4 µM/year). Multivariate analyses suggested that older age, higher systolic blood pressure, and worse BCVA were associated with a lower SH level. Neither the univariate nor multivariate analyses, except between female sex and higher dROM level, were associated with the dROM or BAP level. A lower serum SH level was the driver of aging itself and age-related decline in VA due to cataract. The serum SH level may be an excellent predictor of aging status in each subject.

16.
Int Ophthalmol ; 43(4): 1261-1274, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36173547

RESUMO

PURPOSE: To explore the regulatory effect of miR-125a-3p on lens epithelial cells (LECs) under ultraviolet radiation B (UVB) irradiation. METHODS: The expression of miR-125a-3p in age-related cataract (ARC) specimens and cell models was detected by qRT-PCR. UVB was utilized to establish DNA damage model of LECs. Cell count kit-8 was applied in detecting cell viability. Cell apoptosis ratio was analyzed by flow cytometry. Dual luciferase reports were applied to analyze the mechanism between miRNA and target genes. Nanoparticle tracking analysis, and Western blot were used to identify whether the exosomes were typical exosomes. RESULTS: miR-125a-3p was upregulated in ARC tissues and LECs treated with UVB. Knockdown of miR-125a-3p in LECs significantly decreased apoptosis and increased viability of UVB-irradiated LECs. We predicted that miR-125a-3p could regulate transmembrane Bax inhibitor motif containing 4 (TMBIM4) by the bioinformatics databases TargetScan, miRBase, and miRWalk. Luciferase reporter assays demonstrated that miR-125a-3p may suppress TMBIM4 protein translation by binding to 3'UTR of TMBIM4 mRNA. Overexpression of miR-125a-3p decreased TMBIM4, which suggested that miR-125a-3p could inhibit TMBIM4. Moreover, knockdown of TMBIM4 decreased cell viability and enhanced cell apoptosis during UVB irradiation. In addition, the exosome secretion of LECs irradiated by UVB was enhanced, and the expression of miR-125a-3p was high. Cell viability was significantly decreased, and cell apoptosis was increased during UVB-exos treatment. CONCLUSION: This study indicated that miR-125a-3p regulated apoptosis by suppressing TMBIM4 in LECs under oxidative damage, providing a new idea for clinical therapeutic target of cataract.


Assuntos
Catarata , MicroRNAs , Humanos , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia , Raios Ultravioleta , Transdução de Sinais , MicroRNAs/genética , MicroRNAs/metabolismo , Células Epiteliais , Catarata/genética , Catarata/metabolismo , Apoptose , Proliferação de Células , Proteínas de Membrana/metabolismo
17.
Arch Biochem Biophys ; 723: 109255, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35452623

RESUMO

Age-related cataract (ARC) is a severe visual impairment disease and its pathogenesis remains unclear. This study investigated the relevance of MST2/YAP1/GLUT1 in ARC development in vivo and in vitro, and explored the role and possible mechanisms of this pathway in oxidative damage-mediated apoptosis of lens epithelial cells (LECs). Western blot analysis and immunohistochemistry showed that MST2 and phosphorylated (p)-YAP (Ser127) protein levels were increased, and YAP1 and GLUT1 protein levels were decreased in LECs of ARC patients and aged mice. Additionally, differential expression of MST2 and YAP1 was associated with H2O2-induced apoptosis of human lens epithelial B3 (HLE-B3) cells. CCK-8 and Hoechst 33,342 apoptosis assays showed that MST2 and YAP1 were involved in H2O2-induced apoptosis of LECs. Subsequent experiments showed that, during MST2-mediated H2O2-induced apoptosis, p-YAP (Ser127) levels were elevated and immunofluorescence revealed nucleoplasmic translocation and inhibition of YAP1 protein expression. Furthermore, GLUT1 was in turn synergistically transcriptionally regulated by YAP1-TEAD1 in dual luciferase reporter assays. In conclusion, our study indicates that the MST2/YAP1/GLUT1 pathway plays a major role in the pathogenesis of ARC and LECs apoptosis, providing a new direction for future development of targeted inhibitors that block this signaling pathway to prevent, delay, or even cure ARC.


Assuntos
Catarata , Cristalino , Serina-Treonina Quinase 3/metabolismo , Animais , Apoptose , Catarata/metabolismo , Células Epiteliais/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Camundongos , Estresse Oxidativo , Proteínas de Sinalização YAP
18.
Ophthalmic Physiol Opt ; 42(5): 998-1008, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35690924

RESUMO

PURPOSE: To compare the binocular vision status of patients pre- and post-cataract surgery, and to investigate the risk factors for patients who develop binocular vision anomalies post-surgery. METHODS: A prospective study of patients (≥50 years) who elected to undergo bilateral cataract surgery was implemented. A comprehensive binocular vision test battery including stereopsis, ocular alignment, fusional vergence, vergence facility, near point of convergence and the Convergence Insufficiency Symptom Survey (CISS) was administered before the first surgery and at the third visit after surgery on the second eye. A detailed diagnostic classification protocol was applied to identify the presence of binocular vision anomalies pre- and post-surgery. RESULTS: Seventy-three participants were included at baseline, 24 (33%) of whom were diagnosed with non-strabismic binocular vision anomalies (NSBVA), mainly convergence insufficiency (18/73, 25%). Fifty-one participants completed the post-operative evaluation, 17 (33%) of whom had NSBVA pre-surgery and 13 (26%) post-surgery (p = 0.48). There were a number of conversions from NSBVA to normal binocular vision and vice versa. Logistic regression showed that the adjusted odds ratio of pre-existing NSBVA diagnosis for predicting the risk of post-operative NSBVA was 6.37 (p < 0.01). There were no significant changes in most binocular vision measures post-surgery, except for a significant improvement in the CISS score (p < 0.01, Cohen's d = 0.83). CONCLUSIONS: Binocular vision anomalies, especially convergence insufficiency, are prevalent in the age-related cataract population. Cataract surgery does not appear to be a significant risk factor for the development of new binocular vision anomalies. A pre-existing binocular vision anomaly is the main risk factor for predicting a post-operative binocular vision anomaly in this population.


Assuntos
Catarata , Transtornos da Motilidade Ocular , Acomodação Ocular , Catarata/complicações , Convergência Ocular , Humanos , Transtornos da Motilidade Ocular/diagnóstico , Estudos Prospectivos , Transtornos da Visão/diagnóstico , Visão Binocular
19.
Acta Clin Croat ; 60(3): 441-449, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35282473

RESUMO

This study was designed to explore practical differences between visual acuity (VA) scores measured on Snellen chart versus ETDRS chart, to grade cataracts using LOCS III system, and to compare VA on both charts depending on cataract grade and type. Prospective evaluation of uncorrected and best-corrected visual acuity was carried out on the eye scheduled for cataract surgery preoperatively and postoperatively on the Snellen and ETDRS charts. The study was carried out at Department of Eye Diseases, Clinical Center of Serbia, during a two-year period. Inclusion criteria were met by 540 patients who underwent testing, surgery, data collection and analysis. The mean VA score was better on ETDRS than on Snellen chart. The mean difference was 6.05 letters or 1.21 lines. VA results correlated with all types of cataract regardless of the chart used, with the highest statistical significance (p<0.0001) for subcapsular cataract. The ETDRS chart was found to be more discriminative and precise than Snellen chart, especially for poor VA.


Assuntos
Catarata , Testes Visuais , Catarata/complicações , Humanos , Exame Neurológico , Transtornos da Visão , Testes Visuais/métodos , Acuidade Visual
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