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.

scholarly journals Inhibition of mitochondrial fission preserves photoreceptors after retinal detachment

2017 ◽  
Author(s):  
Xiangjun She ◽  
Xinmin Lu ◽  
Tong Li ◽  
Junran Sun ◽  
Jian Liang ◽  
...  
Keyword(s):  
Vision Loss ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Mitochondrial Fission ◽  
Critical Role ◽  
Photoreceptor Degeneration ◽  
Apoptotic Pathway ◽  
Neurosensory Retina

AbstractPhotoreceptor degeneration is a leading cause of visual impairment worldwide. Separation of neurosensory retina from the underlying retinal pigment epithelium is a prominent feature preceding photoreceptor degeneration in a variety of retinal diseases. Although ophthalmic surgeries have been well developed to restore retinal structures, post-op patients usually experience progressive photoreceptor degeneration and irreversible vision loss that is incurable at present. Previous studies point to a critical role of mitochondria-mediated apoptotic pathway in photoreceptor degeneration, but the upstream triggers remain largely unexplored. In this study, we show that after experimental RD induction, photoreceptors activate dynamin-related protein 1 (Drp1)-dependent mitochondrial fission pathway and subsequent apoptotic cascades. Mechanistically, endogenous ROS is necessary for Drp1 activation in vivo and exogenous ROS insult is sufficient to activate Drp1-dependent mitochondrial fission in cultured photoreceptors. Accordingly, inhibition of Drp1 activity effectively preserves mitochondrial integrity and rescues photoreceptors. Collectively, our data delineates a ROS-Drp1-mitochondria axis that promotes photoreceptor degeneration in retinal diseased models.

scholarly journals Histamine causes an imbalance between pro-angiogenic and anti-angiogenic factors in the retinal pigment epithelium of diabetic retina via H4 receptor/p38 MAPK axis

2020 ◽  
Vol 8 (2) ◽  
pp. e001710
Author(s):  
Byung Joo Lee ◽  
Hye Eun Byeon ◽  
Chang Sik Cho ◽  
Young Ho Kim ◽  
Jin Hyoung Kim ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Retinal Pigment Epithelium ◽  
Regulatory Mechanism ◽  
Histidine Decarboxylase ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Angiogenic Factors ◽  
Mitogen Activated Protein Kinase ◽  
Patients With Diabetes

IntroductionSystemic histaminergic activity is elevated in patients with diabetes mellitus. There are a few studies suggesting that histamine is implicated in the pathogenesis of diabetes, but the exact role of histamine in the development of diabetic retinopathy is unclear. The aim of this study was to investigate the role of histamine receptor H4 (HRH4) in the regulation of retinal pigment epithelium (RPE)-derived pro-angiogenic and anti-angiogenic factors under diabetic conditions.Research design and methodsThe levels of vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), histamine and histidine decarboxylase (HDC) in the serum and vitreous samples of patients with diabetes were compared with those of patients without diabetes. The effect of hyperglycemia on expression levels of HRH4, VEGF, IL-6 and pigment epithelium-derived factor (PEDF) in the RPE was determined. The role of HRH4 in high glucose-induced regulation of VEGF, IL-6 and PEDF in ARPE-19 cells and the underlying regulatory mechanism were verified using an RNA interference-mediated knockdown study.ResultsThe serum and vitreous levels of VEGF, IL-6, histamine and HDC were more increased in patients with diabetic retinopathy than in patients without diabetes. HRH4 was overexpressed in RPE both in vitro and in vivo. Histamine treatment upregulated VEGF and IL-6 and downregulated PEDF expression in ARPE-19 cells cultivated under hyperglycemic conditions. Hyperglycemia-induced phosphorylation of p38 and subsequent upregulation of VEGF and IL-6 and downregulation of PEDF were dampened by small interfering RNA-mediated knockdown of HRH4 in ARPE-19 cells.ConclusionsTaken together, HRH4 was a critical regulator of VEGF, IL-6 and PEDF in the RPE under hyperglycemic conditions and the p38 mitogen-activated protein kinase pathway mediated this regulatory mechanism.

scholarly journals Iron Overload in Diabetic Retinopathy: A Cause or a Consequence of Impaired Mechanisms?

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Andreea Ciudin ◽  
Cristina Hernández ◽  
Rafael Simó
Keyword(s):  
Diabetic Retinopathy ◽  
Iron Overload ◽  
Iron Homeostasis ◽  
Cell Function ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Renin Angiotensin System ◽  
Retinal Neurodegeneration ◽  
Novel Therapeutic Strategies

Iron is an essential ion for life, playing a central role in many metabolic processes. The most important property of free iron is its capacity to be reversibly oxidized and reduced, but at same time this make it highly pro-oxidant molecule. In this regard, iron is able to generate powerful reactive oxygen species (ROS). For this reason, careful control on iron availability is central to the maintenance of normal cell function in the retina. In the diabetic eye there is an impairment of iron homeostasis, thus leading to iron overload. The mechanisms involved in this process include: (1) Destruction of heme molecules induced by hyperglycemia (2) Intraretinal and vitreal hemorrhages (3) Overexpression of the renin-angiotensin system. The main consequences of iron overload are the following: (1) Retinal neurodegeneration due to the increase of oxidative stress (2) Increase of AGE-RAGE binding (3) Defective phagocytosis of retinal pigment epithelium, which generates the accumulation of autoantigens and the synthesis of proinflammatory cytokines. Further studies addressed to explore not only the role of iron in the pathogenesis of diabetic retinopathy, but also to design novel therapeutic strategies based on the regulation of iron homeostasis are needed.

scholarly journals Puerarin protects the retinal pigment epithelium (ARPE19) against hypoxia-induced blood-retinal barrier breakdown and Akt/Bcl2-dependent apoptosis

2021 ◽  
Author(s):  
Minh-Anh Nguyen Ngo Le ◽  
Yao-Tseng Wen ◽  
Dieu-Thuong Thi Trinh ◽  
Rong - Kung Tsai
Keyword(s):  
Retinal Pigment Epithelium ◽  
Group Treatment ◽  
Brain Injuries ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Annexin V ◽  
Blood Retinal Barrier ◽  
Hypoxic Conditions ◽  
Barrier Breakdown ◽  
Induced Apoptosis

Abstract Background: Puerarin, an isoflavonoid, is a neuroprotectant against many ischemic brain injuries. The research purpose was to investigate whether puerarin treatment can inhibit hypoxia-induced apoptosis and barrier breakdown on human retinal pigment epithelium (ARPE-19) cells.Methods: Treatment with 100 µM of puerarin showed no ARPE-19 cytotoxicity. Treatments with 50 µM or 100 µM of puerarin significantly preserved cell viability under hypoxic conditions for 12 h (p < 0.05). Moreover, treatments with 50 µM and 100 µM of puerarin significantly reduced the proportion of Annexin V- and PI-positive ARPE cells under hypoxic conditions (p < 0.05). The TER analysis and junctional protein staining demonstrated that treatments with 50 µM or 100 µM of puerarin prevented the hypoxia-induced barrier disruption in APRE-19 cultures. In contrast to the untreated group, treatment with puerarin significantly increased the level of Bcl-2 and decreased the levels of p-Bad, Bax, and cleaved caspase 3 in RPE cell under hypoxic conditions (p < 0.05). Treatment with puerarin maintained Akt1 activation in the ARPE-19 cells under hypoxic conditions (p < 0.05), and inhibition of PR-induced Akt1 activation abolished the protective effect of puerarin in ARPE-19 cells under hypoxic conditions.Conclusion: Our results demonstrated that treatment with puerarin protected RPE cell against hypoxia-induced blood-retinal barrier breakdown and Akt-dependent apoptosis. These findings suggest that puerarin could be developed as an alternative treatment for ischemic and hypoxic retinal injuries.

VISUAL OUTCOME IN DIABETIC MACULAR EDEMA AFTER GRID LASER TREATMENT

2016 ◽  
Vol 23 (04) ◽  
pp. 478-483
Author(s):  
Muhmmad Jameel Shahid ◽  
Faheem Ahmad ◽  
Muhammad Asif ◽  
Muhmmad Nabeel Sultan
Keyword(s):  
Diabetic Retinopathy ◽  
Macular Edema ◽  
Diabetic Macular Edema ◽  
Laser Photocoagulation ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Case Series ◽  
Visual Outcome ◽  
Blood Retinal Barrier ◽  
Department Of Ophthalmology

Regarding the causes of blindness, Diabetic retinopathy is a one the majorcause of blindness in all types persons from both industrialized and developing countries.Due to inadequate eating habits, prevalence of diabetic retinopathy is increasing. Both focaland diffuse leakage from retinal capillaries can cause Diabetic macular edema. Varioustreatment modalities for macular photocoagulation are focal laser, Grid laser and modified gridused in patients having diabetic macular edema Study Design: Prospective, interventional,noncompetitive case series. Setting: Department of Ophthalmology, Allied Hospital andDepartment of Ophthalmology, Divisional Headquarter Hospital Faisalabad. Period: One yearfrom April 2012 to April 2013. Materials and Methods: A total of 200 eyes of 200 patientswith clinical significant macular edema that met the inclusion criteria were enrolled. Results: Inthis study, 200 patients with diabetic macular edema were studied. Of these 121 (60.5%) weremales and 79 (39.5%) females with mean age of 38.52 years (SD 7.512, Range 25-50 years).All patients had diffuse, clinically significant macular edema at baseline for which they hadreceived grid laser photocoagulation. Discussion: In recent past number of diabetic patientsall over the world has increased that has caused increase incident of diabetic retinopathy .Soin patients having diabetic retinopathy, macular edema can cause deterioration in visual acuityduring any stage of diabetic retinopathy. The pathogenesis of Diabetic macular edema (DME)is the disruption of inner blood – retinal barrier that is known to be associated with metabolicalteration affecting the retinal pigment epithelium or retinal vascular endothelium. Focal and/orgrid laser photocoagulation is being considered as the treatment of DME. Conclusion: Macularphotocoagulation was found to be an effective method of treatment for CSME among diabeticpatients, which has resulted in a positive visual outcome in 87% of the patients (stable andimproved vision).

scholarly journals Immune Privilege: The Microbiome and Uveitis

2021 ◽  
Vol 11 ◽  
Author(s):  
Christine Mölzer ◽  
Jarmila Heissigerova ◽  
Heather M. Wilson ◽  
Lucia Kuffova ◽  
John V. Forrester
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Posterior Uveitis ◽  
Immune Privilege ◽  
Blood Retinal Barrier ◽  
Uveal Tract ◽  
Immune Mediated ◽  
Infectious Uveitis ◽  
Brb Breakdown ◽  
The Brain

Immune privilege (IP), a term introduced to explain the unpredicted acceptance of allogeneic grafts by the eye and the brain, is considered a unique property of these tissues. However, immune responses are modified by the tissue in which they occur, most of which possess IP to some degree. The eye therefore displays a spectrum of IP because it comprises several tissues. IP as originally conceived can only apply to the retina as it contains few tissue-resident bone-marrow derived myeloid cells and is immunologically shielded by a sophisticated barrier – an inner vascular and an outer epithelial barrier at the retinal pigment epithelium. The vascular barrier comprises the vascular endothelium and the glia limitans. Immune cells do not cross the blood-retinal barrier (BRB) despite two-way transport of interstitial fluid, governed by tissue oncotic pressure. The BRB, and the blood-brain barrier (BBB) mature in the neonatal period under signals from the expanding microbiome and by 18 months are fully established. However, the adult eye is susceptible to intraocular inflammation (uveitis; frequency ~200/100,000 population). Uveitis involving the retinal parenchyma (posterior uveitis, PU) breaches IP, while IP is essentially irrelevant in inflammation involving the ocular chambers, uveal tract and ocular coats (anterior/intermediate uveitis/sclerouveitis, AU). Infections cause ~50% cases of AU and PU but infection may also underlie the pathogenesis of immune-mediated “non-infectious” uveitis. Dysbiosis accompanies the commonest form, HLA-B27–associated AU, while latent infections underlie BRB breakdown in PU. This review considers the pathogenesis of uveitis in the context of IP, infection, environment, and the microbiome.

scholarly journals Revisiting the role of Dcc in visual system development with a novel eye clearing method

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Robin J Vigouroux ◽  
Quénol Cesar ◽  
Alain Chédotal ◽  
Kim Tuyen Nguyen-Ba-Charvet
Keyword(s):  
Ganglion Cells ◽  
System Development ◽  
Pigment Epithelium ◽  
Large Fraction ◽  
Retinal Pigment ◽  
Critical Role ◽  
Retinal Ganglion ◽  
Visual System Development ◽  
Deleted In Colorectal Carcinoma

The Deleted in Colorectal Carcinoma (Dcc) receptor plays a critical role in optic nerve development. Whilst Dcc is expressed postnatally in the eye, its function remains unknown as Dcc knockouts die at birth. To circumvent this drawback, we generated an eye-specific Dcc mutant. To study the organization of the retina and visual projections in these mice, we also established EyeDISCO, a novel tissue clearing protocol that removes melanin allowing 3D imaging of whole eyes and visual pathways. We show that in the absence of Dcc, some ganglion cell axons stalled at the optic disc, whereas others perforated the retina, separating photoreceptors from the retinal pigment epithelium. A subset of visual axons entered the CNS, but these projections are perturbed. Moreover, Dcc-deficient retinas displayed a massive postnatal loss of retinal ganglion cells and a large fraction of photoreceptors. Thus, Dcc is essential for the development and maintenance of the retina.

Sign in / Sign up

Export Citation Format

Share Document