Case report: Blindness associated with Learedius learedi trematode infection in a green sea turtle, Chelonia mydas, of the northern Red Sea

Spirorchiid blood flukes are widespread in sea turtles, causing disease and mortality in their populations, with high prevalence in several ocean basins. Besides being leading parasitic causes of sea turtle strandings in several parts of the world, these infectious agents can cause endocarditis, vasculitis, thrombosis, miliary egg granulomas, and aneurysms, which ultimately may compromise the survival of green sea turtles. More severe cases may also result in multifocal granulomatous meningitis or pneumonia, both of which can be fatal. Herein, we report the first case of severe trematode infection, Caused by Learedius learedi, in a green sea turtle in the northern Red Sea; this infection is associated with bilateral blindness. Necropsy revealed multiple granulomas with intralesional trematode eggs in the optic nerve, eyes, spleen, heart, and lungs. The parasite was identified as Learedius learedi through specific primers of the ribosomal genome and COI sequences obtained from GenBank. Altogether, these findings emphasize the importance of recognizing the systemic nature of this particular fluke infection to ultimately protect the lives of these marine animals and ensure the sustainability of these species in the wild

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Changes in Retinal Function and Cellular Remodeling Following Experimental Retinal Detachment in a Rabbit Model

Purpose. To explore functional electroretinographic (ERG) changes and associated cellular remodeling following experimental retinal detachment in a rabbit model. Methods. Retinal detachment was created in ten rabbits by injecting 0.1 ml balanced salt solution under the retina. Fundus imaging was performed 0, 3, 7, 14, and 21 days postoperatively. ERGs were recorded pre- and 7 and 21 days postoperatively. Eyes were harvested on day 21 and evaluated immunohistochemically (IHC) for remodeling of second- and third-order neurons. Results. Retinal reattachment occurred within two weeks following surgery. No attenuation was observed in the photopic or scotopic a- and b-waves. A secondary wavefront on the descending slope of the scotopic b-wave was the only ERG result that was attenuated in detached retinas. IHC demonstrated anatomical changes in both ON and OFF bipolar cells. Bassoon staining was observed in the remodeled dendrites. Amacrine and horizontal cells did not alter, but Muller cells were clearly reactive with marked extension. Conclusion. Retinal detachment and reattachment were associated with functional and anatomical changes. Exploring the significance of the secondary scotopic wavefront and its association with the remodeling of 2nd- and 3rd-order neurons will shade more light on functional changes and recovery of the retina

Transcleral approach for closing retinal tears using DuraSeal™ hydrogel sealant

Purpose: The aim of this study was to evaluate an innovative approach for closing retinal tears using DuraSeal™ (DS) hydrogel sealant in a rabbit model. Methods: Retinal detachment with a small tear was performed on 20 New Zealand rabbits. Thereafter, rabbits were divided into two groups; the experimental group received a transscleral injection of 0.1 ml DS into the subretinal space whereas the control group received sham injection of saline. Eyes were clinically evaluated using indirect ophthalmoscopy, retinal function was recorded in ten rabbits by electroretinography and the sealant's toxicity was evaluated histopathologically. Results: We found that the DS hydrogel was easily injected transsclerally into the subretinal space of the detached retinas with no major complications. Retinal reattachment was seen in both groups within 2 weeks with no toxicity to the sensory retina. There were no significant differences in retinal function between groups. Conclusion: Subretinal injection of hydrogel through a transscleral route is easy to perform and may open a new avenue in the treatment of retinal detachment. However, the efficacy of the DS as a tamponade for sealing retinal tear is yet to be definite. Long-term clinical, functional, and toxicological studies are needed to evaluate its full potential for clinical applications

Extracellular Vesicles Isolated from Equine Adipose-Derived Stromal Stem Cells (ASCs) Mitigate Tunicamycin-Induced ER Stress in Equine Corneal Stromal Stem Cells (CSSCs)

Corneal ulcers, characterized by severe inflammation of the cornea, can lead to serious, debilitating complications and may be vision-threatening for horses. In this study, we aimed to investigate the role of endoplasmic reticulum (ER) stress in corneal stem progenitor cell (CSSC) dysfunction and explore the potential of equine adipose-derived stromal stem cell (ASC)-derived extracellular vesicles (EVs) to improve corneal wound healing. We showed that CSSCs expressed high levels of CD44, CD45, and CD90 surface markers, indicating their stemness. Supplementation of the ER-stress-inducer tunicamycin to CSSCs resulted in reduced proliferative and migratory potential, accumulation of endoplasmic reticulum (ER)-stressed cells in the G0/G1 phase of the cell cycle, increased expression of proinflammatory genes, induced oxidative stress and sustained ER stress, and unfolded protein response (UPR). Importantly, treatment with EVs increased the proliferative activity and number of cells in the G2/Mitosis phase, enhanced migratory ability, suppressed the overexpression of proinflammatory cytokines, and upregulated the anti-inflammatory miRNA-146a-5p, compared to control and/or ER-stressed cells. Additionally, EVs lowered the expression of ER-stress master regulators and effectors (PERK, IRE1, ATF6, and XBP1), increased the number of mitochondria, and reduced the expression of Fis-1 and Parkin, thereby promoting metabolic homeostasis and protecting against apoptosis in equine CSSCs. Our findings demonstrate that MSCs-derived EVs represent an innovative and promising therapeutic strategy for the transfer of bioactive mediators which regulate various cellular and molecular signaling pathways

Immunostaining of distinct neuronal populations of the retina of apoE3 and apoE4 mice.

<p>Retinal sections were stained with the following neuron-specific markers: Recoverin (photoreceptors), CHX10 (pan bipolar cells), PKCα (rod bipolar), DAPI (ganglion cells), Calbindin (Horizontal cells), and PAX6 (amacrine cells) as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064949#s2" target="_blank">Materials and Methods</a>. Representative sections are presented in the upper panel. Retinal borders are marked with white dashed lines, and the specific cells are marked with arrows. Scale bar = 50 µm. The results (mean ± SEM, n = 10) are shown in the lower panel and are presented relative to the apoE3 mice whose values were set as 100%.</p

The effects of apoE4 on retinal nerve terminals.

<p>(A) Immunohistohemistry of retinal sections that were stained by the pan presynaptic marker synaptophysin and for the glutamatergic, GABAergic and cholinergic presynaptic vesicular transporters VGluT1, VGaT and VAChT, respectively, as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0064949#s2" target="_blank">Materials and Methods</a>. Representative sections are depicted on the upper panel. Scale bar = 80 µm for Synaptophysin and 50 µm for VGluT1, VGaT and VAChT. Quantification of the VGluT1, VGaT and VAChT results (mean ± SEM, n = 10) is shown in the lower panel, and is represented relative to the apoE3 mice whose values were set as 100%. (B) Immunoblots of synaptophysin (Syp), VGluT1, and VGaT of retinal homogenates of apoE3 and apoE4. Representative blots are depicted on the left panels, and quantification of these results (mean ± SEM, n = 10) relative to the apoE3 mice is depicted on the right panel. (C) The ratio of VGluT1/VGaT of each mouse in both immunohistochemistry and western blots. (*P<0.03, **P<0.001). (D) Immunoblots of the post-synaptic markers PSD-95 and Gephyrin, of retinal homogenates of apoE3 and apoE4. Representative blots are depicted on the left panels, and quantification of these results and the ratio of PSD95/Gephyrin of each mouse (mean ± SEM, n = 10) relative to the apoE3 mice is depicted on the right panel.</p