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Autophagy facilitates age-related cell apoptosis-a new insight from senile cataract.

ABSTRACT: Age-related cell loss underpins many senescence-associated diseases. Apoptosis of lens epithelial cells (LECs) is the important cellular basis of senile cataract resulted from prolonged exposure to oxidative stress, although the specific mechanisms remain elusive. Our data indicated the concomitance of high autophagy activity, low SQSTM1/p62 protein level and apoptosis in the same LEC from senile cataract patients. Meanwhile, in primary cultured LECs model, more durable autophagy activation and more obvious p62 degradation under oxidative stress were observed in LECs from elder healthy donors, compared with that from young healthy donors. Using autophagy-deficiency HLE-B3 cell line, autophagy adaptor p62 was identified as the critical scaffold protein sustaining the pro-survival signaling PKCι-IKK-NF-κB cascades, which antagonized the pro-apoptotic signaling. Moreover, the pharmacological inhibitor of autophagy, 3-MA, significantly inhibited p62 degradation and rescued oxidative stress-induced apoptosis in elder LECs. Collectively, this study demonstrated that durable activation of autophagy promoted age-related cell death in LECs. Our work contributes to better understanding the pathogenesis of senescence-associated diseases.

SUBMITTER: Huang J

PROVIDER: S-EPMC8748728 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Delay in seeking medical services is common in elderly populations, which leads to disease progression and life difficulty. This study aims to assess the prevalence of delay in medical visits and treatment and define associated effects and factors in patients with senile cataract, which may help obtain a better understanding of late-life psychopathology and provide the basis for interventions. Patients aged more than 60 years were prospectively recruited in Zhongshan Ophthalmic Center (ZOC). All participants were diagnosed with binocular senile cataract and decided to have primary surgery in ZOC. The distributions of the popularity of delaying outpatient visits and treatment, the degrees of visual impairment, the influences on quality of life, and the reasons for delaying treatment among participants were accessed by the descriptive statistics. Factors associated with the perceptions of cataract treatment were accessed using a binary logistic regression model. A total of 400 senile patients aged from 60 to 94 years were enrolled. At diagnosis, 82 (20.5%) participants had a low vision with monocular acuity of both eyes below 0.05. All participants have felt that their normal lives were affected, and 64 (16%) participants felt that their lives were affected severely. Only 17 (4.25%) participants have sought for medical services immediately after feeling vision loss, and 294 (73.50%) participants have felt vision loss since a year ago before seeking medical help. A total of 298 (74.50%) participants have delayed the surgery time, and 229 (57.25%) patients delayed it for more than 12 months. There were 147 (36.75%) participants delaying surgery on account of no knowledge about it and 114 (28.50%) participants delaying surgery because of fear. There are a high proportion of elderly patients with senile cataract delaying their outpatient visits and surgery treatment, whose normal lives were severely affected. Increasing medical service propaganda about cataract and other common diseases in elderly populations would probably be helpful for improving perceptions of diseases and decreasing medical delays. Public needs to draw more attention to the healthy and medical status of the elderly ocular patients.

Project description:ObjectiveWe investigated whether previously reported single nucleotide polymorphisms (SNPs) of EPHA2 in European studies are associated with cataract in India.MethodsWe carried out a population-based genetic association study. We enumerated randomly sampled villages in two areas of north and south India to identify people aged 40 and over. Participants attended a clinical examination including lens photography and provided a blood sample for genotyping. Lens images were graded by the Lens Opacification Classification System (LOCS III). Cataract was defined as a LOCS III grade of nuclear ≥4, cortical ≥3, posterior sub-capsular (PSC) ≥2, or dense opacities or aphakia/pseudophakia in either eye. We genotyped SNPs rs3754334, rs7543472 and rs11260867 on genomic DNA extracted from peripheral blood leukocytes using TaqMan assays in an ABI 7900 real-time PCR. We used logistic regression with robust standard errors to examine the association between cataract and the EPHA2 SNPs, adjusting for age, sex and location.Results7418 participants had data on at least one of the SNPs investigated. Genotype frequencies of controls were in Hardy-Weinberg Equilibrium (p>0.05). There was no association of rs3754334 with cataract or type of cataract. Minor allele homozygous genotypes of rs7543472 and rs11260867 compared to the major homozygote genotype were associated with cortical cataract, Odds ratio (OR) = 1.8, 95% Confidence Interval (CI) (1.1, 3.1) p = 0.03 and 2.9 (1.2, 7.1) p = 0.01 respectively, and with PSC cataract, OR = 1.5 (1.1, 2.2) p = 0.02 and 1.8 (0.9, 3.6) p = 0.07 respectively. There was no consistent association of SNPs with nuclear cataract or a combined variable of any type of cataract including operated cataract.ConclusionsOur results in the Indian population agree with previous studies of the association of EPHA2 variants with cortical cataracts. We report new findings for the association with PSC which is particularly prevalent in Indians.

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Autophagy facilitates age-related cell apoptosis-a new insight from senile cataract.

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