Loss of idiopathic retinal ganglion cells (RGcs) leads to irreversible vision defects and is considered the primary characteristic of glaucoma. However, effective treatment strategies in terms of RGc neuroprotection remain elusive. In the present study, the protective effects of resveratrol on RGc apoptosis, and the mechanisms underlying its effects were investigated, with a particular emphasis on the function of optic atrophy 1 (Opa1). In an ischemia/reperfusion (I/R) injury model, the notable thinning of the retina, significant apoptosis of RGcs, reduction in Opa1 expression and long Opa1 isoform to short Opa1 isoform ratios (L-Opa1/S-Opa1 ratio) were observed, all of which were reversed by resveratrol administration. Serum deprivation resulted in reductions in R28 cell viability, superoxide dismutase (SOd) activity, Opa1 expression and induced apoptosis, which were also partially reversed by resveratrol treatment. To conclude, results from the present study suggest that resveratrol treatment significantly reduced retinal damage and RGc apoptosis in I/R injury and serum deprivation models. In addition, resveratrol reversed the downregulated expression of Opa1 and reduced SOd activity. Mechanistically, resveratrol influenced mitochondrial dynamics by regulating the L-Opa1/S-Opa1 ratio. Therefore, these observations suggest that resveratrol may exhibit potential as a therapeutic agent for RGc damage in the future.
Aging-related retinal degeneration can manifest as decreased visual function due to damage to retinal structures and dysfunction in retinal homeostasis. Naringenin, a flavonoid, has beneficial effects in preventing cellular aging, preserving the functionality of photoreceptors, and slowing down visual function loss. However, the role and potential mechanism of naringenin in the aging mouse retina require further investigation. In this study, we evaluated the effects of naringenin on the aging eye using electroretinogram (ERG) and hematoxylin and eosin staining and explored its potential mechanism by western blotting. ERG showed that naringenin increased the amplitude of the a- and b-waves of scotopic 3.0, 10.0, and the a-wave amplitude of photopic 3.0 in the aging mouse retina. Furthermore, administration of naringenin prevented aging-induced retinal degeneration in the total retina, ganglion cell, inner plexiform layer, inner nuclear layer, and outer nuclear layer. The expression of mitochondrial fusion protein two was increased, OPA1 protein expression and the ratio of L-OPA1/S-OPA1 were unchanged, and dynamin-related protein one was decreased in the 12-month-old mice treated with naringenin compared with the 12-month-old mice treated with vehicle. Furthermore, the downregulation of age-related alterations in autophagy was significantly rescued in the aging mice by treatment with naringenin. Taken together, these results suggest that the oral administration of naringenin improves visual function, retinal structure, mitochondrial dynamics, and autophagy in the aging mouse retinas. Naringenin may be a potential dietary supplement for the prevention or treatment of aging-related retinal degeneration.
Sirtuin 4 (SIRT4) is one of seven mammalian sirtuins that possesses ADP-ribosyltransferase, lipoamidase and deacylase activities and plays indispensable role in metabolic regulation. However, the role of SIRT4 in the retina is not clearly understood. The purpose of this study was to explore the location and function of SIRT4 in the retina. Therefore, immunofluorescence was used to analyze the localization of SIRT4 in rat, mouse and human retinas. Western blotting was used to assess SIRT4 and glutamine synthetase (GS) protein expression at different developmental stages in C57BL/6 mice retinas. We further analyzed the retinal structure, electrophysiological function and the expression of GS protein in SIRT4-deficient mice. Excitotoxicity was caused by intravitreal injection of glutamate (50 nmol) in mice with long-term intraperitoneal injection of resveratrol (20 mg/Kg), and then retinas were subjected to Western blotting and paraffin section staining to analyze the effect of SIRT4 on excitotoxicity. We show that SIRT4 co-locates with Müller glial cell markers (GS and vimentin). The protein expression pattern of SIRT4 was similar to that of GS, and both increased with development. There were no significant retinal structure or electrophysiological function changes in 2-month SIRT4-deficient mice, while the expression of GS protein was decreased. Moreover, long-term administration of resveratrol can upregulate the expression of SIRT4 and GS while reducing the retinal injury caused by excessive glutamate. These results suggest that SIRT4 is highly expressed in retinal Müller glial cells and is relevant to the expression of GS. SIRT4 does not appear to be essential in retinal development, but resveratrol, as an activator of SIRT4, can upregulate GS protein expression and protect the retina from excitotoxicity.
Background This study aimed to assess the fertility intentions of young people after the announcement of the three–child policy in China and to determine whether knowledge about reproductive, maternal, newborn, and child health (RMNCH) services or support, childbearing- and childbirth-related anxiety, and parenthood–related anxiety influence fertility intentions. Methods A cross-sectional Internet-based survey was conducted on a nationwide sample of young people aged 18 to 28 years old in education institutions. Factors associated with fertility intentions were analysed using partial least squares structural equation modelling (PLS-SEM). Results Only 4.2% of males and 1.7% of females intended to have three children or more. On the whole, the majority (40.3%) reported the intention to have two children. The mean and standard deviation (SD) for the total knowledge RMNCH support and/or services knowledge score was 9.5 (SD ± 8.9), out of a possible score of 39. The median and interquartile range (IQR) of childbearing– and childbirth-related anxiety score was 8.0 (IQR = 6.0–9.0), out of a possible score of 10. The median and IQR of parenthood–related anxiety score among the males was 6.0 (IQR = 4.0–9.0) and for females was 7.0 (IQR = 5.0–9.0). Results from PLS-SEM revealed that a higher level of knowledge of RMNCH support and/or services is significantly associated with higher fertility intentions. Both childbearing- and childbirth-related anxiety and parenthood–related anxiety were inversely associated with fertility intentions. Conclusion Raising awareness about RMNCH supportive measures and easing birth- and parenting anxiety are imperative to enhance birth rates. Future policies should pay more attention to these determinants to achieve their intended goal of boosting population growth.
Müller glial cells (MGCs) are a group of glial cells in the retina that provide essential support to retinal neurons; however, the understanding of MGC apoptosis and autophagy remains limited. This study was aimed at investigating the role of autophagy in MGCs under normal and oxidative conditions, and identifying the underlying mechanisms. In addition, the sirtuin 4 (SIRT4)-mediated signaling pathway was observed to regulate the autophagic process in MGCs. To assess the effect of autophagy on MGC mitochondrial function and survival, we treated rMC-1 cells—rat-derived Müller glial cells—with rapamycin and 3-methyladenine (3-MA), and found that MGC death was not induced by such treatment, while autophagic dysfunction could increase MGC apoptosis under oxidative stress, as reflected by the expression level of cleaved caspase 3 and PI staining. In addition, the downregulation of autophagy by 3-MA could influence the morphology of the mitochondrial network structure, the mitochondrial membrane potential, and generation of reactive oxygen species (ROS) under oxidative stress. Moreover, SIRT4 depletion enhanced autophagosome formation, as verified by an increase in the LC3 II/I ratio and a decrease in the expression of SQSTM1/p62, and vice versa. The inhibition of AMPK phosphorylation by compound C could reverse these changes in LC3 II/I and SQSTM1/p62 caused by SIRT4 knockdown. Our research concludes that MGCs can endure autophagic dysfunction in the absence of oxidative stress, while the downregulation of autophagy can cause MGCs to become more sensitized to oxidative stress. Simultaneous exposure to oxidative stress and autophagic dysfunction in MGCs can result in a pronounced impairment of cell survival. Mechanically, SIRT4 depletion can activate the autophagic process in MGCs by regulating the AMPK–mTOR signaling pathway.
A multifunctional platform (PVA@rGO-Ag/5-Fu) integrated with photothermal, antibacterial and drug delivery abilities is developed. The experiments proved that PVA@rGO-Ag/5-Fu has potential as an efficacious anti-scarring agent for filtering surgery.
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