scholarly journals Cone Rescue with Laser Photobiomodulation in Murine and Human Retinal Dystrophy

Author(s):  
Robert J Casson ◽  
John P. M. Wood ◽  
Jack Ao ◽  
Jagjit Gilhotra ◽  
Shane Durkin ◽  
...  

Retinitis pigmentosa (RP) encompasses a genetically diverse group of blinding inherited retinal diseases. In most subtypes the gene defect is expressed in the rod photoreceptors, yet in many affected individuals the cone photoreceptors undergo secondary degeneration, leading to loss of the remaining central vision. There is evidence that bioenergetic and oxidative stress are involved in this secondary cone loss. Photobiomodulation (PBM) uses low energy light in the far red or near-infrared spectrum to manipulate cellular activity. We have used a novel slit lamp-mounted retinal PBM laser to deliver precise energy levels to targeted retina. We showed that PBM laser attenuates oxidative and bioenergetic stress-induced photoreceptor loss in vitro and rescues cones in the rd1 murine model of RP. In a phase I trial (ACTRN12618000651280), foveal laser treatment was safe in humans with RP and temporarily recovered, on average, 5 letters of visual acuity.

Author(s):  
Mazen S. Albaghdadi ◽  
Ryutaro Ikegami ◽  
Mohamad B. Kassab ◽  
Joseph A. Gardecki ◽  
Mie Kunio ◽  
...  

Objective: Near-infrared autofluorescence (NIRAF) of atherosclerosis associates with intraplaque hemorrhage and is detectable in living patients with coronary artery disease. However, further mechanisms underlying NIRAF generation have not been fully characterized. Here, we investigated the role of lipids and oxidative stress in NIRAF generation in atherosclerosis and in vitro in human macrophages. Approach and Results: In N=15 human carotid endarterectomy specimens, we investigated the spatial distribution of lipid, intraplaque hemorrhage, and NIRAF (ex/em 630/650 nm). Plaque NIRAF associated with both Sudan black (SB)-positive lipids ( r =0.53, P =0.023) and GPA (glycophorin A)-positive intraplaque hemorrhage ( r =0.48, P =0.043). Plaque NIRAF also localized with lipid and specifically insoluble lipid (ceroid) and iron. Intriguingly, some NIRAF-positive areas were Sudan black-positive but GPA-negative. Studies on human macrophages investigated further the role of lipids in NIRAF generation. OxLDL (Oxidized low-density lipoprotein) and hemoglobin, but not LDL, generated NIRAF in both THP-1 cells and monocyte-derived macrophages. In oxLDL-treated THP-1 cells, higher NIRAF, lipid peroxidation products, and intracellular oxidative stress markers evolved ( P <0.001 versus LDL). The antioxidants α-tocopherol and N-acetylcysteine suppressed NIRAF generation and oxidative stress. Conclusions: In human atherosclerosis and human macrophages in vitro, NIRAF colocalizes with lipid and specifically insoluble lipid or ceroid. In vitro studies further show that oxidized LDL generates NIRAF, oxidative stress, and lipid peroxidation products. These results demonstrate a new pathway for NIRAF generation through oxidized lipid-driven oxidative stress and support ceroid as a source of NIRAF in human atherosclerosis. These findings may inform future clinical intracoronary NIRAF imaging studies of patients with coronary artery disease.


Author(s):  
S Farahani ◽  
N Riyahi Alam ◽  
S Haghgoo ◽  
M Khoobi ◽  
Gh Geraily ◽  
...  

Background: Numerous unique characteristics of the nanosized gold, including high atomic number, low toxicity, and high biocompatibility make it one of the most appropriate nanostructures to boost radiotherapy efficacy. Many in-vivo and in-vitro investigations have indicated that gold nanoparticles (AuNPs) can significantly increase tumor injuries in low kilovoltage radiotherapy. While deep-lying tumors require much higher energy levels with greater penetration power, and investigations carried out in megavoltage energy range show contradictory results.Objective: In this study, we quantitatively assess and compare dose enhancement factors (DEFs) obtained through AuNPs under radiation of Cobalt-60 source (1.25MeV) versus Iridium-192 source (0.380 KeV) using MAGAT gel dosimeter.Material and Methods: MAGAT polymer gel in both pure and combined with 0.2 mM AuNPs was synthesized. In order to quantify the effect of energy on DEF, irradiation was carried out by Co-60 external radiotherapy and Ir-192 internal radiotherapy. Finally, readings of irradiated and non-irradiated gels were performed by MR imaging.Result: The radiation-induced R2 (1/T2) changes of the gel tubes doped with AuNPs compared to control samples, upon irradiation of beams released by Ir-192 source showed a significant dose enhancement (15.31% ±0.30) relative to the Co-60 external radiotherapy (5.85% ±0.14).Conclusion: This preliminary study suggests the feasibility of using AuNPs in radiation therapy (RT), especially in low-energy sources of brachytherapy. In addition, MAGAT polymer gel, as a powerful dosimeter, could be used for 3D visualization of radiation dose distribution of AuNPs in radiotherapy.


Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 507
Author(s):  
Rosaria Meccariello ◽  
Stefania D’Angelo

Aging and, particularly, the onset of age-related diseases are associated with tissue dysfunction and macromolecular damage, some of which can be attributed to accumulation of oxidative damage. Recently, growing interest has emerged on the beneficial effects of plant-based diets for the prevention of chronic diseases including obesity, diabetes, and cardiovascular disease. Several studies collectively suggests that the intake of polyphenols and their major food sources may exert beneficial effects on improving insulin resistance and related diabetes risk factors, such as inflammation and oxidative stress. They are the most abundant antioxidants in the diet, and their intake has been associated with a reduced aging in humans. Polyphenolic intake has been shown to be effective at ameliorating several age-related phenotypes, including oxidative stress, inflammation, impaired proteostasis, and cellular senescence, both in vitro and in vivo. In this paper, effects of these phytochemicals (either pure forms or polyphenolic-food) are reviewed and summarized according to affected cellular signaling pathways. Finally, the effectiveness of the anti-aging preventive action of nutritional interventions based on diets rich in polyphenolic food, such as the diets of the Blue zones, are discussed.


2020 ◽  
Vol 6 (3) ◽  
pp. 410-413
Author(s):  
Petra J. Kluger ◽  
Svenja Nellinger ◽  
Simon Heine ◽  
Ann-Cathrin Volz

AbstractThe extracellular matrix (ECM) naturally surrounds cells in humans, and therefore represents the ideal biomaterial for tissue engineering. ECM from different tissues exhibit different composition and physical characteristics. Thus, ECM provides not only physical support but also contains crucial biochemical signals that influence cell adhesion, morphology, proliferation and differentiation. Next to native ECM from mature tissue, ECM can also be obtained from the in vitro culture of cells. In this study, we aimed to highlight the supporting effect of cell-derived- ECM (cdECM) on adipogenic differentiation. ASCs were seeded on top of cdECM from ASCs (scdECM) or pre-adipocytes (acdECM). The impact of ECM on cellular activity was determined by LDH assay, WST I assay and BrdU assay. A supporting effect of cdECM substrates on adipogenic differentiation was determined by oil red O staining and subsequent quantification. Results revealed no effect of cdECM substrates on cellular activity. Regarding adipogenic differentiation a supporting effect of cdECM substrates was obtained compared to control. With these results, we confirm cdECM as a promising biomaterial for adipose tissue engineering.


2021 ◽  
Vol 96 ◽  
pp. 107593
Author(s):  
Yiming Ma ◽  
Lijuan Luo ◽  
Xiangming Liu ◽  
Herui Li ◽  
Zihang Zeng ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryoichi Katsube ◽  
Kazuhiro Noma ◽  
Toshiaki Ohara ◽  
Noriyuki Nishiwaki ◽  
Teruki Kobayashi ◽  
...  

AbstractCancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.


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