Introduction: Prostaglandin analogs are the first line of treatment in patients with glaucoma. Recently, many preservative-free prostaglandin analogs have been marketed to increase their tolerance in chronic use. However, potentially safer formulations have been reported to induce inflammation within ocular surface and adnexa, associated with pronounced activation of tissue macrophages. Aim: We aimed to evaluate the effect of a Stearoyl-CoA desaturase-1 (SCD1) inhibitor, MF-438, on the differentiation of monocytes exposed to eye drop detergents, representing saturated fatty acid derivatives. Methods: A culture of human peripheral blood monocytes was exposed to eye drops containing fatty acid derivatives (eye drop detergents), pf-latanoprost (Monoprost ® , hydroxystearate macrogolglycerol -MGHS40) or pf-tafluprost (Taflotan ® , polysorbate 80 -PS80), as well as pf-latanoprost+MF-438, MGHS40, and PS80. For the negative control C(-), monocytes were cultured in basal medium, and for the positive controls, monocytes were stimulated with Lipopolysaccharide (LPS) and Interferon γ (IFNγ) (M1 macrophages) or Interleukin-4 (IL-4) (M2 macrophages). The concentration of desaturase in the cell homogenates was determined by ELISA. The number of cells was counted under a microscope at 20x magnification. Results:The following concentrations of SCD1 (ng/mL) were measured: 7.
IntroductionELAVL1/HuR is a keystone regulator of gene expression at the posttranscriptional level, including stress response and homeostasis maintenance. The aim of this study was to evaluate the impact of hur silencing on the age-related degeneration of retinal ganglion cells (RGC), which potentially describes the efficiency of endogenous neuroprotection mechanisms, as well as to assess the exogenous neuroprotection capacity of hur-silenced RGC in the rat glaucoma model.MethodsThe study consisted of in vitro and in vivo approaches. In vitro, we used rat B-35 cells to investigate, whether AAV-shRNA-HuR delivery affects survival and oxidative stress markers under temperature and excitotoxic insults. In vivo approach consisted of two different settings. In first one, 35 eight-week-old rats received intravitreal injection of AAV-shRNA-HuR or AAV-shRNA scramble control. Animals underwent electroretinography tests and were sacrificed 2, 4 or 6 months after injection. Retinas and optic nerves were collected and processed for immunostainings, electron microscopy and stereology. For the second approach, animals received similar gene constructs. To induce chronic glaucoma, 8 weeks after AAV injection, unilateral episcleral vein cauterization was performed. Animals from each group received intravitreal injection of metallothionein II. Animals underwent electroretinography tests and were sacrificed 8 weeks later. Retinas and optic nerves were collected and processed for immunostainings, electron microscopy and stereology.ResultsSilencing of hur induced apoptosis and increased oxidative stress markers in B-35 cells. Additionally, shRNA treatment impaired the cellular stress response to temperature and excitotoxic insults. In vivo, RGC count was decreased by 39% in shRNA-HuR group 6 months after injection, when compared to shRNA scramble control group. In neuroprotection study, the average loss of RGCs was 35% in animals with glaucoma treated with metallothionein and shRNA-HuR and 11.4% in animals with glaucoma treated with metallothionein and the scramble control shRNA. An alteration in HuR cellular content resulted in diminished photopic negative responses in the electroretinogram.ConclusionsBased on our findings, we conclude that HuR is essential for the survival and efficient neuroprotection of RGC and that the induced alteration in HuR content accelerates both the age-related and glaucoma-induced decline in RGC number and function, further confirming HuR’s key role in maintaining cell homeostasis and its possible involvement in the pathogenesis of glaucoma.
Right hemicolectomy (RH) is a common procedure for both benign and malignant colic disease. Different anastomotic types are performed during this procedure. To assess the association between anastomotic type and postoperative complications (PC) in patients undergoing RH. Retrospective analysis of medical records of 72 patients (39 female and 33 male), aged 24 to 93, undergoing open RH in the Department of Gastrointestinal Surgery. Data regarding anastomotic type [end-to-end anastomosis, side-to-side (SSA), end-to-side anastomosis, and side-to-end anastomosis (SEA)], and different clinical factors were collected. There were 21 (29%) end-to-end anastomosis, 25 (35%) SSA, 15 (21%) end-to-side anastomosis, and 11 (15%) SEA in the analyzed group. Adenocarcinoma G2 was the most frequent indication for RH - 30 (42%). Total duration of hospitalization (in days) was the longest (14, 26) after SEA and the shortest (12, 68) after SSA. PC were noted in 17(24%) patients. Wound infection was the most common complication noted in 15(21%) patients. The overall anastomotic leak rate was 7% (5/72). PC were the most frequent after SEA noted in 64% (7/11) including abdominal bleeding and bowel perforation. The overall reoperations rate was 6% (4/72). The overall mortality rate was 4% (3/72). SEA was associated with the highest incidence of postoperative complication however based on this and other studies there are no satisfying conclusions regarding the best choice of anastomosis.
Deficiency of estradiol during the menopausal period is an important risk factor for neurodegenerative diseases, including various optic neuropathies. The aim of this study was to evaluate the impact of surgical menopause on the function and survival ratio of RGCs in the rat model of ONC (optic nerve crush). We used eight-week-old female Long Evans rats, divided into two main groups depending on the time between ovariectomy procedure (OVA) and euthanasia (two weeks vs. seven weeks), and subgroups—OVA, OVA + ONC, or ONC. Retinal function was assessed with electroretinography (ERG). RGC loss ratio was evaluated using immunolabelling and counting of RGCs. Seven weeks after OVA, the menopause morphologically affected interneurons but not RGC; however, when the ONC procedure was applied, RGCs appeared to be more susceptible to damage in case of deprivation of estrogens. In our analysis, PhNR (photopic negative responses) were severely diminished in the OVA + ONC group. A deprivation of estrogens in menopause results in accelerated retinal neurodegeneration that firstly involves retinal interneurons. The lack of estrogens increases the susceptibility of RGCs to insults.
Purpose To evaluate the impact of oral treatment with SSRI – escitalopram (EC) on the function of interneurons (IN) assessed in electroretinography. Methods Six Long Evans rats were treated orally with SSRI‐escitalopram (n=3) or phosphate buffered saline‐PBS (n=3) for 6 weeks daily. After 4 weeks transient elevation of intraocular pressure (IOP) was inducted in the right eye of every rat in order to induce retinal ischemia (IC). Electroretinography (ERG) was performed using Celeris device and oscillatory potentials were analysed (OPs) in 4 time points ‐ before drug administration, before IC induction and 7 & 14 days after it. After 6 weeks rats were sacrificed, retinas were isolated in order to conduct the histological assessment and cell counts. Western Blot analysis was performed in order to assess BDNF and connexin 36 content in retinas and brains. Results The mean peak IOP was 24 mmHg in the right eye and 12 mmHg in the left eye and was similar in treated and control groups. In both groups no loss of RGC density was noted between the eye with induced IC and the healthy one (80 ± 31 vs 76 ± 20 cells/visual field for EC and 55 ± 10 vs 55 ± 11 for PBS; p > 0.05). In the functional measurements in the EC group amplitudes of all scotopic OPs (OP1‐5) were significantly higher 14 days after IC induction when compared to control group (p < 0.05), where deep disturbance of IN function was observed, specifically for OP2‐4, expressed in significant reduction of OP amplitudes (p < 0.05). Similar changes were not observed in photopic conditions. Conclusions Oral treatment with EC prevents desynchronization of retinal IN function during ischemic conditions in a rat. Observations presented above may become crucial for new therapeutic methods for vascular pathologies of the retina.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.