scholarly journals Zinc and Diabetic Retinopathy

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao Miao ◽  
Weixia Sun ◽  
Lining Miao ◽  
Yaowen Fu ◽  
Yonggang Wang ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Age Related Macular Degeneration ◽  
Ocular Tissue ◽  
Zn Deficiency ◽  
Ocular Development ◽  
Age Related ◽  
Negative Effect ◽  
High Concentrations ◽  
Available Information

Zinc (Zn) is an important nutrient that is involved in various physiological metabolisms. Zn dyshomeostasis is often associated with various pathogeneses of chronic diseases, such as metabolic syndrome, diabetes, and related complications. Zn is present in ocular tissue in high concentrations, particularly in the retina and choroid. Zn deficiencies have been shown to affect ocular development, cataracts, age-related macular degeneration, and even diabetic retinopathy. However, the mechanism by which Zn deficiency increases the prevalence of diabetic retinopathy remains unclear. In addition, due to the negative effect of Zn deficiency on the eye, Zn supplementation should prevent diabetic retinopathy; however, limited available data do not always support this notion. Therefore, the goal of this paper was to summarize these pieces of available information regarding Zn prevention of diabetic retinopathy. Current theories and possible mechanisms underlying the role of Zn in the eye-related diseases are discussed. The possible factors that affect the preventive effect of Zn supplementation on diabetic retinopathy were also discussed.

scholarly journals Empowering Mesenchymal Stem Cells for Ocular Degenerative Disorders

2019 ◽  
Vol 20 (7) ◽  
pp. 1784 ◽  
Author(s):  
Ding ◽  
Subbiah ◽  
Khan ◽  
Farhana ◽  
Mok
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Diabetic Retinopathy ◽  
Age Related Macular Degeneration ◽  
Ocular Tissue ◽  
Clinical Settings ◽  
Age Related ◽  
Degenerative Disorders ◽  
Therapeutic Outcomes ◽  
Multipotent Mesenchymal Stem Cells

Multipotent mesenchymal stem cells (MSCs) have been employed in numerous pre-clinical and clinical settings for various diseases. MSCs have been used in treating degenerative disorders pertaining to the eye, for example, age-related macular degeneration, glaucoma, retinitis pigmentosa, diabetic retinopathy, and optic neuritis. Despite the known therapeutic role and mechanisms of MSCs, low cell precision towards the targeted area and cell survivability at tissue needing repair often resulted in a disparity in therapeutic outcomes. In this review, we will discuss the current and feasible strategy options to enhance treatment outcomes with MSC therapy. We will review the application of various types of biomaterials and advances in nanotechnology, which have been employed on MSCs to augment cellular function and differentiation for improving treatment of visual functions. In addition, several modes of gene delivery into MSCs and the types of associated therapeutic genes that are important for modulation of ocular tissue function and repair will be highlighted.

scholarly journals Involvement of Nrf2 in Ocular Diseases

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Shehzad Batliwala ◽  
Christy Xavier ◽  
Yang Liu ◽  
Hongli Wu ◽  
Iok-Hou Pang
Keyword(s):  
Oxidative Stress ◽  
Diabetic Retinopathy ◽  
Macular Degeneration ◽  
Human Body ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Checks And Balances ◽  
Age Related ◽  
The World

The human body harbors within it an intricate and delicate balance between oxidants and antioxidants. Any disruption in this checks-and-balances system can lead to harmful consequences in various organs and tissues, such as the eye. This review focuses on the effects of oxidative stress and the role of a particular antioxidant system—the Keap1-Nrf2-ARE pathway—on ocular diseases, specifically age-related macular degeneration, cataracts, diabetic retinopathy, and glaucoma. Together, they are the major causes of blindness in the world.

scholarly journals Eph Receptors and Ephrins in Retinal Diseases

2021 ◽  
Vol 22 (12) ◽  
pp. 6207
Author(s):  
Radoslaw Kaczmarek ◽  
Pawel Gajdzis ◽  
Malgorzata Gajdzis
Keyword(s):  
Diabetic Retinopathy ◽  
Retinopathy Of Prematurity ◽  
The Elderly ◽  
Common Point ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Eph Receptors ◽  
Age Related ◽  
The Common

Retinal diseases are the leading cause of irreversible blindness. They affect people of all ages, from newborns in retinopathy of prematurity, through age-independent diabetic retinopathy and complications of retinal detachment, to age-related macular degeneration (AMD), which occurs mainly in the elderly. Generally speaking, the causes of all problems are disturbances in blood supply, hypoxia, the formation of abnormal blood vessels, and fibrosis. Although the detailed mechanisms underlying them are varied, the common point is the involvement of Eph receptors and ephrins in their pathogenesis. In our study, we briefly discussed the pathophysiology of the most common retinal diseases (diabetic retinopathy, retinopathy of prematurity, proliferative vitreoretinopathy, and choroidal neovascularization) and collected available research results on the role of Eph and ephrins. We also discussed the safety aspect of the use of drugs acting on Eph and ephrin for ophthalmic indications.

scholarly journals Role of Ocular Angiogenic Factors in the Development of Neovascular Age-Related Macular Degeneration

2020 ◽  
Vol 74 (3) ◽  
pp. 159-164
Author(s):  
Elīza Briede ◽  
Kristīne Baumane ◽  
Angelika Krūmiņa
Keyword(s):  
Macular Degeneration ◽  
Treatment Options ◽  
Angiogenic Factors ◽  
Age Related Macular Degeneration ◽  
Fluid Accumulation ◽  
Hard Exudate ◽  
Abnormal Growth ◽  
Age Related ◽  
Available Information

AbstractAge-related macular degeneration (AMD) is a progressive degenerative eye disease. Neovascular age-related macular degeneration (nAMD) is the advanced form of AMD characterised by abnormal growth of newly formed blood vessels in chorioidea which typically involves fluid accumulation in the retina or retinal haemorrhage, retinal epithelial detachments, hard exudate or subretinal scars. The process of angiogenesis is controlled by ocular angiogenic factors, which have enabled the development of different treatment options aimed at these factors. This review aims to compile the available information about the most commonly identified ocular angiogenic factors, uncovering their role in the pathogenesis of nAMD and assessing their application possibilities as biomarkers of disease identification and treatment.

scholarly journals Systemic exposure following intravitreal administration of therapeutic agents: an integrated pharmacokinetic approach. 2. THR-687

2021 ◽  
Author(s):  
Marc Vanhove ◽  
Jean-Marc Wagner ◽  
Bernard Noppen ◽  
Bart Jonckx ◽  
Elke Vermassen ◽  
...  
Keyword(s):  
General Circulation ◽  
Pharmacokinetic Model ◽  
Systemic Exposure ◽  
Age Related Macular Degeneration ◽  
Whole Body ◽  
Pharmacological Agents ◽  
Age Related ◽  
Pharmacokinetic Properties ◽  
High Concentrations ◽  
Systemic Compartment

AbstractIntravitreal (IVT) injection remains the preferred administration route of pharmacological agents intended for the treatment of back of the eye diseases such as diabetic macular edema (DME) and neovascular age-related macular degeneration (nvAMD). The procedure enables drugs to be delivered locally at high concentrations whilst limiting whole body exposure and associated risk of systemic adverse events. Nevertheless, intravitreally-delivered drugs do enter the general circulation and achieving an accurate understanding of systemic exposure is pivotal for the evaluation and development of drugs administered in the eye. We report here the full pharmacokinetic properties of THR-687, a pan RGD integrin antagonist currently in clinical development for the treatment of DME, in both rabbit and minipig. Pharmacokinetic characterization included description of vitreal elimination, of systemic pharmacokinetics, and of systemic exposure following IVT administration. For the latter, we present a novel pharmacokinetic model that assumes clear partition between the vitreous humor compartment itself where the drug is administered and the central systemic compartment. We also propose an analytical solution to the system of differential equations that represent the pharmacokinetic model, thereby allowing data analysis with standard nonlinear regression analysis. The model accurately describes circulating levels of THR-687 following IVT administration in relevant animal models, and we suggest that this approach is relevant to a range of drugs and analysis of subsequent systemic exposure.

scholarly journals Complement C5 is not critical for the formation of sub-RPE deposits in Efemp1 mutant mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Donita L. Garland ◽  
Eric A. Pierce ◽  
Rosario Fernandez-Godino
Keyword(s):  
Macular Degeneration ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Deposit Formation ◽  
Genetic Ablation ◽  
Age Related ◽  
Complement Dysregulation

AbstractThe complement system plays a role in the formation of sub-retinal pigment epithelial (RPE) deposits in early stages of age-related macular degeneration (AMD). But the specific mechanisms that connect complement activation and deposit formation in AMD patients are unknown, which limits the development of efficient therapies to reduce or stop disease progression. We have previously demonstrated that C3 blockage prevents the formation of sub-RPE deposits in a mouse model of EFEMP1-associated macular degeneration. In this study, we have used double mutant Efemp1R345W/R345W:C5-/- mice to investigate the role of C5 in the formation of sub-RPE deposits in vivo and in vitro. The data revealed that the genetic ablation of C5 does not eliminate the formation of sub-RPE deposits. Contrarily, the absence of C5 in RPE cultures promotes complement dysregulation that results in increased activation of C3, which likely contributes to deposit formation even in the absence of EFEMP1-R345W mutant protein. The results also suggest that genetic ablation of C5 alters the extracellular matrix turnover through an effect on matrix metalloproteinases in RPE cell cultures. These results confirm that C3 rather than C5 could be an effective therapeutic target to treat early AMD.

scholarly journals Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 309
Author(s):  
Pachiappan Arjunan ◽  
Radhika Swaminathan ◽  
Jessie Yuan ◽  
Mohamed Elashiry ◽  
Amany Tawfik ◽  
...  
Keyword(s):  
Murine Model ◽  
Retinal Thickness ◽  
Age Related Macular Degeneration ◽  
Periodontal Pathogen ◽  
Fundus Photography ◽  
Mouse Retina ◽  
Rrna Gene ◽  
Age Related ◽  
Periodontal Infection

Emerging evidence underscores an association between age-related macular degeneration (AMD) and periodontal disease (PD), yet the biological basis of this linkage and the specific role of oral dysbiosis caused by PD in AMD pathophysiology remains unclear. Furthermore, a simple reproducible model that emulates characteristics of both AMD and PD has been lacking. Hence, we established a novel AMD+PD murine model to decipher the potential role of oral infection (ligature-enhanced) with the keystone periodontal pathogen Porphyromonas gingivalis, in the progression of neovasculogenesis in a laser-induced choroidal-neovascularization (Li-CNV) mouse retina. By a combination of fundus photography, optical coherence tomography, and fluorescein angiography, we documented inflammatory drusen-like lesions, reduced retinal thickness, and increased vascular leakage in AMD+PD mice retinae. H&E further confirmed a significant reduction of retinal thickness and subretinal drusen-like deposits. Immunofluorescence microscopy revealed significant induction of choroidal/retinal vasculogenesis in AMD+PD mice. qPCR identified increased expression of oxidative-stress, angiogenesis, pro-inflammatory mediators, whereas antioxidants and anti-inflammatory genes in AMD+PD mice retinae were notably decreased. Through qPCR, we detected Pg and its fimbrial 16s-RrNA gene expression in the AMD+PD mice retinae. To sum-up, this is the first in vivo study signifying a role of periodontal infection in augmentation of AMD phenotype, with the aid of a pioneering AMD+PD murine model established in our laboratory.

scholarly journals FHL-1 interacts with human RPE cells through the α5β1 integrin and confers protection against oxidative stress

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rawshan Choudhury ◽  
Nadhim Bayatti ◽  
Richard Scharff ◽  
Ewa Szula ◽  
Viranga Tilakaratna ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Fate ◽  
Retinal Pigment ◽  
Factor H ◽  
Age Related Macular Degeneration ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Rpe Cells ◽  
Age Related

AbstractRetinal pigment epithelial (RPE) cells that underlie the neurosensory retina are essential for the maintenance of photoreceptor cells and hence vision. Interactions between the RPE and their basement membrane, i.e. the inner layer of Bruch’s membrane, are essential for RPE cell health and function, but the signals induced by Bruch’s membrane engagement, and their contributions to RPE cell fate determination remain poorly defined. Here, we studied the functional role of the soluble complement regulator and component of Bruch’s membrane, Factor H-like protein 1 (FHL-1). Human primary RPE cells adhered to FHL-1 in a manner that was eliminated by either mutagenesis of the integrin-binding RGD motif in FHL-1 or by using competing antibodies directed against the α5 and β1 integrin subunits. These short-term experiments reveal an immediate protein-integrin interaction that were obtained from primary RPE cells and replicated using the hTERT-RPE1 cell line. Separate, longer term experiments utilising RNAseq analysis of hTERT-RPE1 cells bound to FHL-1, showed an increased expression of the heat-shock protein genes HSPA6, CRYAB, HSPA1A and HSPA1B when compared to cells bound to fibronectin (FN) or laminin (LA). Pathway analysis implicated changes in EIF2 signalling, the unfolded protein response, and mineralocorticoid receptor signalling as putative pathways. Subsequent cell survival assays using H2O2 to induce oxidative stress-induced cell death suggest hTERT-RPE1 cells had significantly greater protection when bound to FHL-1 or LA compared to plastic or FN. These data show a non-canonical role of FHL-1 in protecting RPE cells against oxidative stress and identifies a novel interaction that has implications for ocular diseases such as age-related macular degeneration.

scholarly journals Bone Morphogenetic Proteins and Diabetic Retinopathy

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 593
Author(s):  
Khaled Elmasry ◽  
Samar Habib ◽  
Mohamed Moustafa ◽  
Mohamed Al-Shabrawey
Keyword(s):  
Diabetic Retinopathy ◽  
Bone Morphogenetic Proteins ◽  
Potential Role ◽  
Microvascular Dysfunction ◽  
Cardiovascular Complications ◽  
Bmp Signaling ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Retinal Inflammation ◽  
Underlying Mechanisms

Bone morphogenetic proteins (BMPs) play an important role in bone formation and repair. Recent studies underscored their essential role in the normal development of several organs and vascular homeostasis in health and diseases. Elevated levels of BMPs have been linked to the development of cardiovascular complications of diabetes mellitus. However, their particular role in the pathogenesis of microvascular dysfunction associated with diabetic retinopathy (DR) is still under-investigated. Accumulated evidence from our and others’ studies suggests the involvement of BMP signaling in retinal inflammation, hyperpermeability and pathological neovascularization in DR and age-related macular degeneration (AMD). Therefore, targeting BMP signaling in diabetes is proposed as a potential therapeutic strategy to halt the development of microvascular dysfunction in retinal diseases, particularly in DR. The goal of this review article is to discuss the biological functions of BMPs, their underlying mechanisms and their potential role in the pathogenesis of DR in particular.

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