Possible Role of Pigment-epithelium-derived Factor in Corneal Angiogenesis

2009 ◽  
Vol 03 (01) ◽  
pp. 64
Author(s):  
Oran Abdiu ◽  
Gysbert Van Setten ◽  
◽  
Keyword(s):  
Growth Factor ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Antiangiogenic Agents ◽  
Special Role ◽  
Corneal Tissue ◽  
Pigment Epithelium Derived Factor ◽  
Corneal Angiogenesis

The detection of pigment-epithelium-derived factor (PEDF) in corneal tissue has allowed greater understanding of the avascularity of corneal tissue. The ability of the cornea to maintain the avascular nature of this tissue, also referred to as the angiogenic privilege of the cornea, could be partly attributed to the presence of this factor. This privilege is severely impaired by various diseases of the ocular surface associated with inflammation and infection that are often followed by neovascularisation, which compromises the transparency of the cornea and results in visual impairment. The rapidly increasing insights into the basic mechanisms controlling neovascularisation, i.e. balance of growth factor activation and enzymatic activity, has most recently led to the development of large-scale use of specific antiangiogenic agents in the treatment of neovascular age-related macular degeneration (AMD). Focusing on the effects of vascular endothelial growth factor (VEGF), the use of such agents, including bevacizumab (Avastin®), a humanised anti-VEGF monoclonal antibody originally used in the treatment of metastatic colorectal cancer, has been investigated in corneal angiogenesis. PEDF is only one of the many factors involved in ocular angiogenesis. However, although it is only a small protein, it has strong antiangiogenic actions that are expressed in the retinal pigment epithelial (RPE) layer, as well as in other parts of the eye. There are specific characteristics that could designate a special role for PEDF in the regulation of avascularity in the eye. In this article, we focus on corneal angiogenesis and highlight the special features of this somewhat unexplored cytokine, outlining the current knowledge and possible role of PEDF in corneal neovascularisation.

scholarly journals Role of Pigment Epithelium-Derived Factor in Stem/Progenitor Cell-Associated Neovascularization

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Jung-Tung Liu ◽  
Yuh-Lien Chen ◽  
Wen-Chi Chen ◽  
Huey-Yi Chen ◽  
Yi-Wen Lin ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Biological Activities ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Antiangiogenic Agents ◽  
Multifunctional Protein ◽  
Pigment Epithelium Derived Factor ◽  
Complex Process ◽  
Epithelium Cells

Pigment epithelium-derived factor (PEDF) was first identified in retinal pigment epithelium cells. It is an endogenously produced protein that is widely expressed throughout the human body such as in the eyes, liver, heart, and adipose tissue; it exhibits multiple and varied biological activities. PEDF is a multifunctional protein with antiangiogenic, antitumorigenic, antioxidant, anti-inflammatory, antithrombotic, neurotrophic, and neuroprotective properties. More recently, PEDF has been shown to be the most potent inhibitor of stem/progenitor cell-associated neovascularization. Neovascularization is a complex process regulated by a large, interacting network of molecules from stem/progenitor cells. PEDF is also involved in the pathogenesis of angiogenic eye disease, tumor growth, and cardiovascular disease. Novel antiangiogenic agents with tolerable side effects are desired for the treatment of patients with various diseases. Here, we review the value of PEDF as an important endogenous antiangiogenic molecule; we focus on the recently identified role of PEDF as a possible new target molecule to influence stem/progenitor cell-related neovascularization.

scholarly journals Subthreshold Nano-Second Laser Treatment and Age-Related Macular Degeneration

2021 ◽  
Vol 10 (3) ◽  
pp. 484
Author(s):  
Amy C. Cohn ◽  
Zhichao Wu ◽  
Andrew I. Jobling ◽  
Erica L. Fletcher ◽  
Robyn H. Guymer
Keyword(s):  
Macular Degeneration ◽  
Laser Treatment ◽  
Short Pulse ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Nanosecond Laser ◽  
Age Related ◽  
Short Pulse Lasers

The presence of drusen is an important hallmark of age-related macular degeneration (AMD). Laser-induced regression of drusen, first observed over four decades ago, has led to much interest in the potential role of lasers in slowing the progression of the disease. In this article, we summarise the key insights from pre-clinical studies into the possible mechanisms of action of various laser interventions that result in beneficial changes in the retinal pigment epithelium/Bruch’s membrane/choriocapillaris interface. Key learnings from clinical trials of laser treatment in AMD are also summarised, concentrating on the evolution of laser technology towards short pulse, non-thermal delivery such as the nanosecond laser. The evolution in our understanding of AMD, through advances in multimodal imaging and functional testing, as well as ongoing investigation of key pathological mechanisms, have all helped to set the scene for further well-conducted randomised trials to further explore potential utility of the nanosecond and other subthreshold short pulse lasers in AMD.

scholarly journals Mechanism of Inflammation in Age-Related Macular Degeneration: An Up-to-Date on Genetic Landmarks

2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Francesco Parmeggiani ◽  
Francesco S. Sorrentino ◽  
Mario R. Romano ◽  
Ciro Costagliola ◽  
Francesco Semeraro ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Complex Disease ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Basic Research ◽  
Cholesterol Homeostasis ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Immune Mediated

Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment among people over 50 years of age, accounting for up to 50% of all cases of legal blindness in Western countries. Although the aging represents the main determinant of AMD, it must be considered a multifaceted disease caused by interactions among environmental risk factors and genetic backgrounds. Mounting evidence and/or arguments document the crucial role of inflammation and immune-mediated processes in the pathogenesis of AMD. Proinflammatory effects secondary to chronic inflammation (e.g., alternative complement activation) and heterogeneous types of oxidative stress (e.g., impaired cholesterol homeostasis) can result in degenerative damages at the level of crucial macular structures, that is photoreceptors, retinal pigment epithelium, and Bruch’s membrane. In the most recent years, the association of AMD with genes, directly or indirectly, involved in immunoinflammatory pathways is increasingly becoming an essential core for AMD knowledge. Starting from the key basic-research notions detectable at the root of AMD pathogenesis, the present up-to-date paper reviews the best-known and/or the most attractive genetic findings linked to the mechanisms of inflammation of this complex disease.

scholarly journals Cell–Matrix Interactions in the Eye: From Cornea to Choroid

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 687
Author(s):  
Andrew E. Pouw ◽  
Mark A. Greiner ◽  
Razek G. Coussa ◽  
Chunhua Jiao ◽  
Ian C. Han ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Transforming Growth Factor Β ◽  
Corneal Dystrophy ◽  
Tissue Growth ◽  
Age Related Macular Degeneration ◽  
Disease States ◽  
Age Related

The extracellular matrix (ECM) plays a crucial role in all parts of the eye, from maintaining clarity and hydration of the cornea and vitreous to regulating angiogenesis, intraocular pressure maintenance, and vascular signaling. This review focuses on the interactions of the ECM for homeostasis of normal physiologic functions of the cornea, vitreous, retina, retinal pigment epithelium, Bruch’s membrane, and choroid as well as trabecular meshwork, optic nerve, conjunctiva and tenon’s layer as it relates to glaucoma. A variety of pathways and key factors related to ECM in the eye are discussed, including but not limited to those related to transforming growth factor-β, vascular endothelial growth factor, basic-fibroblastic growth factor, connective tissue growth factor, matrix metalloproteinases (including MMP-2 and MMP-9, and MMP-14), collagen IV, fibronectin, elastin, canonical signaling, integrins, and endothelial morphogenesis consistent of cellular activation-tubulogenesis and cellular differentiation-stabilization. Alterations contributing to disease states such as wound healing, diabetes-related complications, Fuchs endothelial corneal dystrophy, angiogenesis, fibrosis, age-related macular degeneration, retinal detachment, and posteriorly inserted vitreous base are also reviewed.

Inflammation disrupts epithelial barrier function and induces the release of different populations of exosomes

2020 ◽  
Vol 30 (Supplement_2) ◽  
Author(s):  
B Martins ◽  
T Rodrigues ◽  
J Ramalho ◽  
A Ambrósio ◽  
H Girão ◽  
...  
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Primary Cultures ◽  
Age Related Macular Degeneration ◽  
Relative Role ◽  
Rpe Cells ◽  
Age Related ◽  
Different Populations ◽  
The Impact

Abstract Introduction Age-related macular degeneration (AMD) is a degenerative retinal disease that affects central vision. Most of their phenotypical features are believed to be associated with the dysfunction of retinal pigment epithelium (RPE). The accumulation of damaged proteins in aged RPE is associated with disruption of proteolytic pathways and exocytic activity, with release of intracellular proteins via exosomes (Exo), that are important players in intercellular communication and can contribute to disease progression. However, the impact of their secretion by polarized RPE on outer blood retinal barrier (oBRB) breakdown remains largely elusive Objectives Our aim was to explore the role of inflammation on the loss of RPE integrity and to understand the relative role of directional secretion of Exo by RPE in the loss of polarity and barrier disruption Methodology We used a human RPE cell line (ARPE-19), highly polarized RPE primary cultures (pRPE) and porcine eyecups. To mimic the inflammatory conditions present in AMD, cells were treated with two inflammatory stimuli, TNF (10 ng/mL) or LPS (100 ng/mL) Results TNF and LPS do not affect the viability of the RPE cells. RPE cells developed a confluent monolayer and reached a relatively constant TER of about 40 Ω/cm2 (ARPE-19) or higher than 150 Ω/cm2 (pRPE). Treatment with TNF significantly reduces the TER, decreased immunoreactivity and co-localization of the TJ proteins ZO-1 and occludin and increases MMP-2/-9 activity in the medium. Apical Exo isolated from the RPE cells are enriched in CD63 compared to the basolateral Exo, that are enriched in CD81. The Exo isolated from porcine eyecups, especially with the LPS stimulus, are enriched in CD81 and MMP-2 but have similar levels of CD63 Conclusion Overall, our results show that inflammation induces loss of RPE integrity and release of different populations of Exo. The unravelling of novel drug targets paves the way for development of new therapeutic strategies for AMD.

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