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BMJ Open Ophthalmology Jun 2024Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide. Prompt diagnosis and treatment are crucial in ROP management. Thus, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide. Prompt diagnosis and treatment are crucial in ROP management. Thus, the identification of prominent risk factors could facilitate immediate action. Among various risk factors, the effects of mode of delivery on ROP remain unclear. Therefore, this study aims to assess the association between different modes of delivery on ROP incidence.
METHODS AND ANALYSIS
Comprehensive literature search was conducted on PubMed, ProQuest, EBSCOHost and Cochrane databases, to evaluate the association of mode of delivery-vaginal delivery or caesarean section (c-section)-and the incidence of ROP from inception to December 2023. Random-effects meta-analysis was performed to estimate the pooled OR along with their 95% CIs.
RESULTS
This review included 5 cohort studies involving 2048 babies. A higher incidence of ROP was observed in infants born through vaginal delivery compared with caesarean section. Meta-analysis showed that C-section decreased the unadjusted odds of having ROP infants by 46% with low heterogeneity (OR 0.54 (95% CI 0.40 to 0.73); I=40.73%). However, pooled adjusted effects were statistically insignificant with moderate heterogeneity (adjusted OR 0.59 (95% CI 0.28 to 1.23); I=70.51%), possibly stemming from multiple variations in the controlled variables of each study.
CONCLUSION
Despite varying statistical significance, our findings underscore the crucial need to comprehend the influence of delivery mode on neonatal ophthalmic outcomes. Due to a limited number of existing studies, further research is needed to confirm the association.
PROSPERO REGISTRATION NUMBER
CRD42023486278.
Topics: Humans; Retinopathy of Prematurity; Incidence; Infant, Newborn; Delivery, Obstetric; Female; Risk Factors; Pregnancy; Cesarean Section; Gestational Age
PubMed: 38918018
DOI: 10.1136/bmjophth-2024-001678 -
Journal of Vision Jun 2024A large body of literature has examined specificity and transfer of perceptual learning, suggesting a complex picture. Here, we distinguish between transfer over...
A large body of literature has examined specificity and transfer of perceptual learning, suggesting a complex picture. Here, we distinguish between transfer over variations in a "task-relevant" feature (e.g., transfer of a learned orientation task to a different reference orientation) and transfer over a "task-irrelevant" feature (e.g., transfer of a learned orientation task to a different retinal location or different spatial frequency), and we focus on the mechanism for the latter. Experimentally, we assessed whether learning a judgment of one feature (such as orientation) using one value of an irrelevant feature (e.g., spatial frequency) transfers to another value of the irrelevant feature. Experiment 1 examined whether learning in eight-alternative orientation identification with one or multiple spatial frequencies transfers to stimuli at five different spatial frequencies. Experiment 2 paralleled Experiment 1, examining whether learning in eight-alternative spatial-frequency identification at one or multiple orientations transfers to stimuli with five different orientations. Training the orientation task with a single spatial frequency transferred widely to all other spatial frequencies, with a tendency to specificity when training with the highest spatial frequency. Training the spatial frequency task fully transferred across all orientations. Computationally, we extended the identification integrated reweighting theory (I-IRT) to account for the transfer data (Dosher, Liu, & Lu, 2023; Liu, Dosher, & Lu, 2023). Just as location-invariant representations in the original IRT explain transfer over retinal locations, incorporating feature-invariant representations effectively accounted for the observed transfer. Taken together, we suggest that feature-invariant representations can account for transfer of learning over a "task-irrelevant" feature.
Topics: Humans; Photic Stimulation; Young Adult; Male; Visual Perception; Adult; Female; Transfer, Psychology; Learning; Orientation, Spatial; Computer Simulation; Orientation
PubMed: 38916886
DOI: 10.1167/jov.24.6.17 -
Microbiology Spectrum Jun 2024Tuberculosis (TB) is a leading cause of death among infectious diseases worldwide due to latent TB infection, which is the critical step for the successful pathogenic...
UNLABELLED
Tuberculosis (TB) is a leading cause of death among infectious diseases worldwide due to latent TB infection, which is the critical step for the successful pathogenic cycle. In this stage resides inside the host in a dormant and antibiotic-tolerant state. Latent TB infection can also lead to multisystemic diseases because invades virtually all organs, including ocular tissues. Ocular tuberculosis (OTB) occurs when the dormant bacilli within the ocular tissues reactivate, originally seeded by hematogenous spread from pulmonary TB. Histological evidence suggests that retinal pigment epithelium (RPE) cells play a central role in immune privilege and in protection from antibiotic effects, making them an anatomical niche for invading . RPE cells exhibit high tolerance to environmental redox stresses, allowing phagocytosed bacilli to maintain viability in a dormant state. However, the microbiological and metabolic mechanisms determining the interaction between the RPE intracellular environment and phagocytosed are largely unknown. Here, liquid chromatography-mass spectrometry metabolomics were used to illuminate the metabolic state within RPE cells reprogrammed to harbor dormant bacilli and enhance antibiotic tolerance. Timely and accurate diagnosis as well as efficient chemotherapies are crucial in preventing the poor visual outcomes of OTB patients. Unfortunately, the efficacy of current methods is highly limited. Thus, the results will lead to propose a novel therapeutic option to synthetically kill the dormant inside the RPE cells by modulating the phenotypic state of and laying the foundation for a new, innovative regimen for treating OTB.
IMPORTANCE
Understanding the metabolic environment within the retinal pigment epithelium (RPE) cells altered by infection with and mycobacterial dormancy is crucial to identify new therapeutic methods to cure ocular tuberculosis. The present study showed that RPE cellular metabolism is altered to foster intracellular to enter into the dormant and drug-tolerant state, thereby blunting the efficacy of anti-tuberculosis chemotherapy. RPE cells serve as an anatomical niche as the cells protect invading bacilli from antibiotic treatment. LC-MS metabolomics of RPE cells after co-treatment with HO and infection showed that the intracellular environment within RPE cells is enriched with a greater level of oxidative stress. The antibiotic tolerance of intracellular within RPE cells can be restored by a metabolic manipulation strategy such as co-treatment of antibiotic with the most downstream glycolysis metabolite, phosphoenolpyruvate.
PubMed: 38916325
DOI: 10.1128/spectrum.00788-24 -
Frontiers in Neurology 2024In central retinal artery occlusion (CRAO) or retinal stroke, which is usually a vision-threatening condition, timely diagnosis is imperative to improve the chances of...
In central retinal artery occlusion (CRAO) or retinal stroke, which is usually a vision-threatening condition, timely diagnosis is imperative to improve the chances of retinal preservation and to establish adequate secondary prevention measures. Even though retinal strokes have been traditionally assigned to the field of ophthalmology, while considering reperfusion therapy as the only way to avoid permanent vision loss, we suggest prompt evaluation of CRAO causes (primarily related to cardiovascular risk factors) performed by a well-organized interdisciplinary team (ophthalmologist and neurologist) in a neurovascular center with stroke expertise. Therefore, the most suitable adjunct method for rapidly diagnosing non-arteritic CRAO could be target transorbital ultrasound, performed by an experienced neurologist/neurosonologist in the stroke unit. Consequently, after an ophthalmological assessment, a final decision on thrombolytic therapy could be made. We accept that further research is obviously needed to determine whether transorbital ultrasound could replace ophthalmological investigation in the case of a suspected acute retinal stroke. We assert that retinal stroke requires interdisciplinary treatment in cooperation with neurologists and ophthalmologists, with an additive value for each to achieve the best results for the patient.
PubMed: 38915799
DOI: 10.3389/fneur.2024.1397751 -
BioRxiv : the Preprint Server For... Jun 2024How does evolution act on neuronal populations to match computational characteristics to functional demands? We address this problem by comparing visual code and retinal...
How does evolution act on neuronal populations to match computational characteristics to functional demands? We address this problem by comparing visual code and retinal cell composition in closely related murid species with different behaviours. are diurnal and have substantially thicker inner retina and larger visual thalamus than nocturnal . High-density electrophysiological recordings of visual response features in the dorsal lateral geniculate nucleus (dLGN) reveals that attains higher spatiotemporal acuity both by denser coverage of the visual scene and a selective expansion of elements of the code characterised by non-linear spatiotemporal summation. Comparative analysis of single cell transcriptomic cell atlases reveals that realignment of the visual code is associated with increased relative abundance of bipolar and ganglion cell types supporting OFF and ON-OFF responses. These findings demonstrate how changes in retinal cell complement can reconfigure the coding of visual information to match changes in visual needs.
PubMed: 38915685
DOI: 10.1101/2024.06.14.598659 -
BioRxiv : the Preprint Server For... Jun 2024During development, microglia prune excess synapses to refine neuronal circuits. In neurodegeneration, the role of microglia-mediated synaptic pruning in circuit...
UNLABELLED
During development, microglia prune excess synapses to refine neuronal circuits. In neurodegeneration, the role of microglia-mediated synaptic pruning in circuit remodeling and dysfunction is important for developing therapies aimed at modulating microglial function. Here we analyzed the role of microglia in the synapse disassembly of degenerating postsynaptic neurons in the inner retina. After inducing transient intraocular pressure elevation to injure retinal ganglion cells, microglia increase in number, shift to ameboid morphology, and exhibit greater process movement. Furthermore, due to the greater number of microglia, there is increased colocalization of microglia with synaptic components throughout the inner plexiform layer and with excitatory synaptic sites along individual ganglion cell dendrites. Microglia depletion partially restores ganglion cell function, suggesting that microglia activation may be neurotoxic in early neurodegeneration. Our results demonstrate the important role of microglia in synapse disassembly in degenerating circuits, highlighting their recruitment to synaptic sites early after neuronal injury.
HIGHLIGHTS
Early after transient intraocular pressure elevation: Microglia increase in number, complexity, and process movementMicroglia-synaptic contacts increase in the inner plexiform layerMicroglia-synaptic contacts increase on retinal ganglion cell dendritesMicroglia depletion partially restores ganglion cell function.
PubMed: 38915631
DOI: 10.1101/2024.06.13.598914 -
BioRxiv : the Preprint Server For... Jun 2024Angiogenesis plays a vital role for postnatal development and tissue repair following ischemia. Reactive oxygen species (ROS) generated by NADPH oxidases (NOXes) and...
Angiogenesis plays a vital role for postnatal development and tissue repair following ischemia. Reactive oxygen species (ROS) generated by NADPH oxidases (NOXes) and mitochondria act as signaling molecules that promote angiogenesis in endothelial cells (ECs) which mainly relies on aerobic glycolysis for ATP production. However, the connections linking redox signaling with glycolysis are not well understood. The GTPase Drp1 is a member of the dynamin superfamily that moves from cytosol to mitochondria through posttranslational modifications to induce mitochondrial fission. The role of Drp1 in ROS-dependent VEGF signaling and angiogenesis in ECs has not been previously described. Here, we identify an unexpected function of endothelial Drp1 as a redox sensor, transmitting VEGF-induced H O signals to enhance glycolysis and angiogenesis. Loss of Drp1 expression in ECs inhibited VEGF-induced angiogenic responses. Mechanistically, VEGF rapidly induced the NOX4-dependent sulfenylation (CysOH) of Drp1 on Cys , promoting disulfide bond formation with the metabolic kinase AMPK and subsequent sulfenylation of AMPK at Cys via the mitochondrial fission-mitoROS axis. This cysteine oxidation of AMPK, in turn, enhanced glycolysis and angiogenesis. , mice with EC-specific Drp1 deficiency or CRISPR/Cas9-engineered "redox-dead" (Cys to Ala) Drp1 knock-in mutations exhibited impaired retinal angiogenesis and post-ischemic neovascularization. Our findings uncover a novel role for endothelial Drp1 in linking VEGF-induced mitochondrial redox signaling to glycolysis through a cysteine oxidation-mediated Drp1-AMPK redox relay, driving both developmental and reparative angiogenesis.
PubMed: 38915542
DOI: 10.1101/2024.06.15.599174 -
International Journal of Retina and... Jun 2024The EVA Nexus system offers several technical improvements over its predecessor. The newly designed Aveta cannula system for vitrectomy surgery avoids the need for...
BACKGROUND
The EVA Nexus system offers several technical improvements over its predecessor. The newly designed Aveta cannula system for vitrectomy surgery avoids the need for removal of the valve from the infusion cannula. The chamfered leading edge of the cannula also reduces the insertion force needed. The new EquiPhaco needles in combination with SmartIOP provide excellent anterior chamber stability during phaco-emulsification surgery, enabling to work at lower infusion pressures, and the multiburst phaco mode allows easier removal of hard cataracts. The system offers a secondary active infusion line for independent control of pressure to the anterior and posterior chambers, monitoring of flow rate/reflux and warning of infusion bottle emptying. This study evaluated whether these technical improvements result in improved surgical safety.
METHODS
In total, 250 eyes that underwent vitrectomy (53%) or phaco-vitrectomy (47%) using the EVA Nexus system were prospectively included. The occurrence of intraoperative adverse events was compared to that of historically operated eyes using the EVA system.
RESULTS
The average age of the patients was 63 years. A total of 33% of the patients were operated on for retinal detachment, 17% for macular pucker, 11% for treating floaters, 9% for removing silicone oil, 8% for macular hole repair and 22% for other diseases. In 75% of surgeries, 23 G instruments were used, and 27 G instruments were used in 25% of cases. Device issues that occurred included priming cycle issues (n = 4), eye pressure stability problems (n = 6) and vitrectome performance issues (n = 1), all of which in the first 100 patients who were included and were fixed with software updates. The frequency of surgical complications in the anterior segment was lower than that in the historically recorded surgical reports. Intraoperative events in the posterior segment included hemorrhage from retinal vessels, choroidal hematoma, iatrogenic retinal damage/tear, and subchoroidal infusion. Again, these events occurred rarely and less frequently than in the historical surgical reports.
CONCLUSIONS
The EVA Nexus provides a surgical platform that reduces the incidence of intraoperative adverse events and iatrogenic complications in both anterior and posterior segment surgery. This could increase surgical safety during cataract and vitrectomy surgery. TRIAL REGISTRATION NUMBER CLINICALTRIALS.GOV: : NCT05229094 Data 22/5/2021.
PubMed: 38915097
DOI: 10.1186/s40942-024-00563-3 -
Biological Research Jun 2024Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness....
BACKGROUND
Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness. Nowadays anti-VEGF and retinal photocoagulation are mainstream treatments for ROP, but they develop a variety of complications. Hydrogen (H) is widely considered as a useful neuroprotective and antioxidative therapeutic method for hypoxic-ischemic disease without toxic effects. However, whether H provides physiological angiogenesis promotion, neovascularization suppression and glial protection in the progression of ROP is largely unknown.This study aims to investigate the effects of H on retinal angiogenesis, neovascularization and neuroglial dysfunction in the retinas of oxygen-induced retinopathy (OIR) mice.
METHODS
In this study, mice that were seven days old and either wild-type (WT) or Nrf2-deficient (Nrf2-/-) were exposed to 75% oxygen for 5 days and then returned to normal air conditions. Different stages of hydrogen gas (H) inhalation were administered. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. To count the number of neovascularization endothelial nuclei, routine HE staining of retinal sections was conducted. Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. Western blots were used to measure the expression of NF-E2-related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), Notch1, Dll4, and HIF-1α. Additionally, the expression of target genes such as NQO1, HO-1, Notch1, Hey1, Hey2, and Dll4 was measured. Human umbilical vein endothelial cells (HUVECs) treated with H under hypoxia were used as an in vitro model. RT-PCR was used to evaluate the mRNA expression of Nrf2, Notch/Dll4, and the target genes. The expression of reactive oxygen species (ROS) was observed using immunofluorescence staining.
RESULTS
Our results indicate that 3-4% H does not disturb retinal physiological angiogenesis, but ameliorates vaso-obliteration and neovascularization in OIR mice. Moreover, H prevents the decreased density and reverses the morphologic and functional changes in retinal astrocytes caused by oxygen-induced injury. In addition, H inhalation reduces microglial activation, especially in the area of neovascularization in OIR mice. H plays a protective role in vascular regeneration by promoting Nrf2 activation and suppressing the Dll4-induced Notch signaling pathway in vivo. Also, H promotes the proliferation of HUVECs under hypoxia by negatively regulating the Dll4/Notch pathway and reducing ROS levels through Nrf2 pathway aligning with our findings in vivo.Moreover, the retinal oxygen-sensing mechanisms (HIF-1α/VEGF) are also involved in hydrogen-mediated retinal revascularization and neovascularization suppression.
CONCLUSIONS
Collectively, our results indicate that H could be a promising therapeutic agent for POR treatment and that its beneficial effect in human ROP might involve the activation of the Nrf2-Notch axis as well as HIF-1α/VEGF pathways.
Topics: Animals; Hydrogen; Oxygen; Retinal Neovascularization; Neuroglia; Mice; Disease Models, Animal; Retinopathy of Prematurity; Mice, Inbred C57BL; Retina; Animals, Newborn; Regeneration; Immunohistochemistry; Retinal Vessels
PubMed: 38915069
DOI: 10.1186/s40659-024-00515-z -
Journal of Neuroinflammation Jun 2024Radiation retinopathy (RR) is a major side effect of ocular tumor treatment by plaque brachytherapy or proton beam therapy. RR manifests as delayed and progressive...
Radiation retinopathy (RR) is a major side effect of ocular tumor treatment by plaque brachytherapy or proton beam therapy. RR manifests as delayed and progressive microvasculopathy, ischemia and macular edema, ultimately leading to vision loss, neovascular glaucoma, and, in extreme cases, secondary enucleation. Intravitreal anti-VEGF agents, steroids and laser photocoagulation have limited effects on RR. The role of retinal inflammation and its contribution to the microvascular damage occurring in RR remain incompletely understood. To explore cellular and vascular events after irradiation, we analyzed their time course at 1 week, 1 month and 6 months after rat eyes received 45 Gy X-beam photons. Müller glial cells, astrocytes and microglia were rapidly activated, and these markers of retinal inflammation persisted for 6 months after irradiation. This was accompanied by early cell death in the outer retina, which persisted at later time points, leading to retinal thinning. A delayed loss of small retinal capillaries and retinal hypoxia were observed after 6 months, indicating inner blood‒retinal barrier (BRB) alteration but without cell death in the inner retina. Moreover, activated microglial cells invaded the entire retina and surrounded retinal vessels, suggesting the role of inflammation in vascular alteration and in retinal cell death. Radiation also triggered early and persistent invasion of the retinal pigment epithelium by microglia and macrophages, contributing to outer BRB disruption. This study highlights the role of progressive and long-lasting inflammatory mechanisms in RR development and demonstrates the relevance of this rat model to investigate human pathology.
Topics: Animals; Rats; Retina; Disease Models, Animal; Retinal Diseases; Inflammation; Radiation Injuries, Experimental; Radiation Injuries; Male; Microglia
PubMed: 38915029
DOI: 10.1186/s12974-024-03151-2