scholarly journals Role of the Blood-Retinal Barrier Transporters: Antiaging in Retina

2021 ◽  
Vol 141 (12) ◽  
pp. 1319-1325
Author(s):  
Ken-ichi Hosoya ◽  
Shin-ichi Akanuma ◽  
Yoshiyuki Kubo
Keyword(s):  
Blood Retinal Barrier

Mechanistic Insights into Immunological Therapy for Targeting Diabetic Retinopathy

2021 ◽  
Vol 5 (3) ◽  
pp. 01-05
Author(s):  
Imteyaz Qamar
Keyword(s):  
Diabetic Retinopathy ◽  
Progressive Disease ◽  
Common Complication ◽  
Blood Retinal Barrier ◽  
Immunological Therapy ◽  
Tnf Α ◽  
Capillary Occlusion ◽  
Inflammatory Molecules ◽  
Inflammatory Effect

Diabetic retinopathy (DR) is a common complication amongst patients that have diabetes. It is a leading cause of blindness in middle age people. A large proportion of patients who have diabetes develop retinopathy. There are several immunological reasons associated with the pathophysiology of this disease. Role of several mediators that increase the oxidative stress and have a pro-inflammatory effect which leads to capillary occlusion and neovascularization (NV). Increased vasopermeability due to disruption of the blood-retinal barrier (BRB) leading to diabetic macular edema (DME). Immunotherapies utilise different compounds and target various inflammatory molecules like TNF-α and pathways such as PPARγ for treatment of this progressive disease. Inflammatory and pro-inflammatory pathways are found to have an essential role in promoting DR; therefore, targeting them provides a useful technique for curing DR.

scholarly journals Uptake Study in Lysosome-Enriched Fraction: Critical Involvement of Lysosomal Trapping in Quinacrine Uptake but Not Fluorescence-Labeled Verapamil Transport at Blood-Retinal Barrier

Pharmaceutics ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 747 ◽  
Author(s):  
Yoshiyuki Kubo ◽  
Miki Yamada ◽  
Saki Konakawa ◽  
Shin-ichi Akanuma ◽  
Ken-ichi Hosoya
Keyword(s):  
Retinal Pigment ◽  
Transport Processes ◽  
Minor Role ◽  
Bafilomycin A1 ◽  
Blood Retinal Barrier ◽  
Retinal Capillary ◽  
Intracellular Compartments ◽  
The Difference ◽  
A Minor

Lysosomal trapping at the blood–retinal barrier (BRB) was investigated through quinacrine and fluorescence-labeled verapamil (EFV) uptake. Quinacrine uptake by conditionally immortalized rat retinal capillary endothelial (TR-iBRB2) cells suggested saturable and non-saturable transport processes in the inner BRB. The reduction of quinacrine uptake by bafilomycin A1 suggested quinacrine distribution to the acidic intracellular compartments of the inner BRB, and this notion was also supported in confocal microscopy. In the study using the lysosome-enriched fraction of TR-iBRB2 cells, quinacrine uptake was inhibited by bafilomycin A1, suggesting the lysosomal trapping of quinacrine in the inner BRB. Pyrilamine, clonidine, and nicotine had no effect on quinacrine uptake, suggesting the minor role of lysosomal trapping in their transport across the inner BRB. Bafilomycin A1 had no effect on EFV uptake, and lysosomal trapping driven by the acidic interior pH was suggested as a minor mechanism for EFV transport in the inner BRB. The minor contribution of lysosomal trapping was supported by the difference in inhibitory profiles between EFV and quinacrine uptakes. Similar findings were observed in the outer BRB study with the fraction of conditionally immortalized rat retinal pigment epithelial (RPE-J) cells. These results suggest the usefulness of lysosome-enriched fractions in studying lysosomal trapping at the BRB.

The role of müller cells in the formation of the blood-retinal barrier

Neuroscience ◽  
1993 ◽  
Vol 55 (1) ◽  
pp. 291-301 ◽  
Author(s):  
S. Tout ◽  
T. Chan-Ling ◽  
H. Holländer ◽  
J. Stone
Keyword(s):  
Müller Cells ◽  
Muller Cells ◽  
Blood Retinal Barrier

scholarly journals Role of vascular endothelial growth factor-165b in the breakdown of the blood-retinal barrier after acute high intraocular pressure in rats

2019 ◽  
Author(s):  
Jing Shen ◽  
Xi-Nan Yi ◽  
Zheng-Hai Liu ◽  
Min Li ◽  
Wei-Xian Liu ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Intraocular Pressure ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Blood Retinal Barrier ◽  
Intravitreous Injection ◽  
Anti Vegf ◽  
Endothelial Growth Factor ◽  
Brb Breakdown

Abstract Background: The blood-retinal barrier (BRB) is essential in maintaining the retinal homeostasis of the microenvironment, previous studies have found that BRB breakdown occurs after acute high intraocular pressure (HIOP) in rats, elevated intraocular pressure can induce upregulation of vascular endothelial growth factor-165b (VEGF-165b) protein in the retina, but the role of VEGF-A165b in BRB breakdown after acute HIOP is still undetermined. Methods: In this study, the rat acute HIOP model was established before and after intravitreous injection of anti-VEGF-165b antibody. The expression of VEGF-165b and ZO-1 in rat retina was detected by immunohistochemistry or western blotting, and the breakdown of BRB was detected by Evans blue (EB) dye. Results: The normal retina of rats expressed VEGF-165b protein, which was mainly located in the retinal ganglion cell (RGC) layer and the inner nuclear layer and was coexpressed with tight junction protein ZO-1. After acute HIOP, the expression of VEGF-165b was upregulated (P < 0.01); The expression of ZO-1 was downregulated (P < 0.01) at 12 h and then recovered at 3 d; EB leakage increased, peaking at 12 h (P < 0.01). After intravitreous injection of anti-VEGF-165b antibody, the expression of VEGF-165b protein was significantly downregulated (P < 0.01); and the downregulation of the expression of ZO-1 was more obvious (P < 0.01); EB leakage became more serious, peaking at 3 d (P < 0.01). EB analysis also showed that EB leakage in the peripheral retina was greater than that in the central retina (P < 0.01). Conclusions: The endogenous VEGF-165b protein may protect the BRB from acute HIOP by regulating the expression of ZO-1. The differential destruction of BRB after acute HIOP may be related to the selective loss of RGCs.

scholarly journals Role of Peoxisome Proliferator Activator Receptor on Blood Retinal Barrier Breakdown

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-4 ◽  
Author(s):  
Yasuo Yanagi
Keyword(s):  
Diabetic Retinopathy ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Critical Role ◽  
Blood Retinal Barrier ◽  
Early Diabetes ◽  
Pathological Conditions ◽  
Barrier Breakdown ◽  
Brb Breakdown

The retinal vessels have two barriers: the retinal pigment epithelium and the retinal vascular endothelium. Each barrier exhibits increased permeability under various pathological conditions. This condition is referred to as blood retinal barrier (BRB) breakdown. Clinically, the most frequently encountered condition causing BRB breakdown is diabetic retinopathy. In recent studies, inflammation has been linked to BRB breakdown and vascular leakage in diabetic retinopathy. Biological support for the role of inflammation in early diabetes is the adhesion of leukocytes to the retinal vasculature (leukostasis) observed in diabetic retinopathy. is a member of a ligand-activated nuclear receptor superfamily and plays a critical role in a variety of biological processes, including adipogenesis, glucose metabolism, angiogenesis, and inflammation. There is now strong experimental evidence to support the theory that inhibits diabetes-induced retinal leukostasis and leakage, playing an important role in the pathogenesis of diabetic retinopathy. Therapeutic targeting of may be beneficial to diabetic retinopathy.

Role of l-Type Amino Acid Transporter 1 at the Inner Blood-Retinal Barrier in the Blood-to-Retina Transport of Gabapentin

2018 ◽  
Vol 15 (6) ◽  
pp. 2327-2337 ◽  
Author(s):  
Shin-ichi Akanuma ◽  
Atsuko Yamakoshi ◽  
Takeshi Sugouchi ◽  
Yoshiyuki Kubo ◽  
Anika M. S. Hartz ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Transporter ◽  
Blood Retinal Barrier ◽  
Acid Transporter

scholarly journals Role of Extracellular Mycobacteria in Blood-Retinal Barrier Invasion in a Zebrafish Model of Ocular TB

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 333
Author(s):  
Santhosh Kumar Damera ◽  
Ranjan Kumar Panigrahi ◽  
Sanchita Mitra ◽  
Soumyava Basu
Keyword(s):  
Immune Cells ◽  
Vascular Endothelium ◽  
Intraocular Inflammation ◽  
Post Injection ◽  
Blood Retinal Barrier ◽  
Zebrafish Model ◽  
Course Of Disease ◽  
Retinal Tissue ◽  
Ocular Tb

Intraocular inflammation following mycobacterial dissemination to the eye is common in tuberculosis (TB)-endemic countries. However, the early host–pathogen interactions during ocular dissemination are unknown. In this study, we investigated the early events during mycobacterial invasion of the blood-retinal barriers (BRBs) with fluorescent-tagged Mycobacterium marinum (Mm), host macrophages, and retinal vasculature in a zebrafish model of ocular TB. We found that Mm invaded the vascular endothelium in either the extracellular or intracellular (inside phagocytes) state, typically 3–4 days post-injection (dpi). Extracellular Mm are phagocytosed in the retinal tissue and progress to form a compact granuloma around 6 dpi. Intracellular Mm crossing the BRBs are likely to be less virulent and either persist inside solitary macrophages (in most cases) or progress to loosely arranged granuloma (rarely). The early interactions between mycobacteria and host immune cells can thus determine the course of disease during mycobacterial dissemination to the eye.

scholarly journals Role of extracellular mycobacteria in blood-retinal barrier invasion in a zebrafish model of ocular TB

2021 ◽  
Author(s):  
Santhosh Kumar Damera ◽  
Ranjan Kumar Panigrahi ◽  
Sanchita Mitra ◽  
Soumyava Basu
Keyword(s):  
Immune Cells ◽  
Vascular Endothelium ◽  
Intraocular Inflammation ◽  
Post Injection ◽  
Blood Retinal Barrier ◽  
Zebrafish Model ◽  
Course Of Disease ◽  
Retinal Tissue ◽  
Ocular Tb

Intraocular inflammation following mycobacterial dissemination to the eye is common in tuberculosis (TB)-endemic countries. However, the early host-pathogen interactions during ocular dissemination are unknown. In this study, we investigate the early events during mycobacterial invasion of the blood-retinal barriers (BRB) with fluorescent tagged  Mycobacterium marinum  ( Mm ), host macrophages and retinal vasculature in a zebrafish model of ocular TB. We found that  Mm  invaded the vascular endothelium either in extracellular or intracellular (inside phagocytes) state, typically 3-4 days post-injection (dpi). Extracellular  Mm  are phagocytosed in the retinal tissue, and progress to form a compact granuloma around 6 dpi. Intracellular  Mm  crossing the BRB are likely to be less virulent, and either persist inside solitary macrophages (most cases), or progress to loosely arranged granuloma (rare). The early interactions between mycobacteria and host immune cells can thus determine the course of disease during mycobacterial dissemination to the eye.

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