scholarly journals Cell Therapy for Retinal Dystrophies: From Cell Suspension Formulation to Complex Retinal Tissue Bioengineering

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Karim Ben M’Barek ◽  
Christelle Monville
Keyword(s):  
Cell Therapy ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Future Research ◽  
Therapeutic Effects ◽  
Primary Defect ◽  
Retinal Tissue ◽  
Age Related

Retinal degeneration is an irreversible phenomenon caused by various disease conditions including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). During the course of these diseases, photoreceptors (PRs) are susceptible to degeneration due to their malfunctions or to a primary dysfunction of the retinal pigment epithelium (RPE). Once lost, these cells could not be endogenously regenerated in humans, and cell therapy to replace the lost cells is one of the promising strategies to recover vision. Depending on the nature of the primary defect and the stage of the disease, RPE cells, PRs, or both might be transplanted to achieve therapeutic effects. We describe in this review the current knowledge and recent progress to develop such approaches. The different cell sources proposed for cell therapy including human pluripotent stem cells are presented with their advantages and limits. Another critical aspect described herein is the pharmaceutical formulation of the end product to be delivered into the eye of patients. Finally, we also outline the future research directions in order to develop a complex multilayered retinal tissue for end-stage patients.

scholarly journals Age-related Macular Degeneration: Current Knowledge of Zinc Metalloproteinases Involvement

2019 ◽  
Vol 20 (9) ◽  
pp. 903-918 ◽  
Author(s):  
Francesca Liva ◽  
Doretta Cuffaro ◽  
Elisa Nuti ◽  
Susanna Nencetti ◽  
Elisabetta Orlandini ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Critical Role ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Tissue Inhibitors Of Metalloproteinase ◽  
Age Related ◽  
A Disintegrin And Metalloproteinase

Background: Advanced age-related macular degeneration (AMD) is the leading cause of blindness in the elderly with limited therapeutic options. The disease is characterized by photoreceptor loss in the macula and reduced Retinal Pigment Epithelium (RPE) function, associated with matrix degradation, cell proliferation, neovascularization and inflammation. Matrix metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play a critical role in the physiology of extracellular matrix (ECM) turnover and, in turn, in ECM pathologies, such as AMD. A balance between the activities of MMPs and Tissue Inhibitors of Metalloproteinase (TIMPs) is crucial for the integrity of the ECM components; indeed, a dysregulation in the ratio of these factors produces profound changes in the ECM, including thickening and deposit formation, which eventually might lead to AMD development. Objective: This article reviews the relevance and impact of zinc metalloproteinases on the development of AMD and their roles as biomarkers and/or therapeutic targets. We illustrate some studies on several inhibitors of MMPs currently used to dissect physiological properties of MMPs. Moreover, all molecules or technologies used to control MMP and ADAM activity in AMD are analyzed. Conclusion: This study underlines the changes in the activity of MMPs expressed by RPE cells, highlights the functions of already used MMP inhibitors and consequently suggests their application as therapeutic agents for the treatment of AMD.

scholarly journals The Cytoskeleton of the Retinal Pigment Epithelium: from Normal Aging to Age-Related Macular Degeneration

2019 ◽  
Vol 20 (14) ◽  
pp. 3578 ◽  
Author(s):  
Ioana-Sandra Tarau ◽  
Andreas Berlin ◽  
Christine A. Curcio ◽  
Thomas Ach
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Complex Structure ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Strong Connection ◽  
Age Related

The retinal pigment epithelium (RPE) is a unique epithelium, with major roles which are essential in the visual cycle and homeostasis of the outer retina. The RPE is a monolayer of polygonal and pigmented cells strategically placed between the neuroretina and Bruch membrane, adjacent to the fenestrated capillaries of the choriocapillaris. It shows strong apical (towards photoreceptors) to basal/basolateral (towards Bruch membrane) polarization. Multiple functions are bound to a complex structure of highly organized and polarized intracellular components: the cytoskeleton. A strong connection between the intracellular cytoskeleton and extracellular matrix is indispensable to maintaining the function of the RPE and thus, the photoreceptors. Impairments of these intracellular structures and the regular architecture they maintain often result in a disrupted cytoskeleton, which can be found in many retinal diseases, including age-related macular degeneration (AMD). This review article will give an overview of current knowledge on the molecules and proteins involved in cytoskeleton formation in cells, including RPE and how the cytoskeleton is affected under stress conditions—especially in AMD.

scholarly journals Microglia Contribution to the Regulation of the Retinal and Choroidal Vasculature in Age-Related Macular Degeneration

Cells ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 1217 ◽  
Author(s):  
C. Henrique Alves ◽  
Rosa Fernandes ◽  
Ana Raquel Santiago ◽  
António Francisco Ambrósio
Keyword(s):  
Macular Degeneration ◽  
Vascular System ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Microglial Cells ◽  
Endothelial Cell Proliferation ◽  
Metabolic Demand ◽  
Age Related

The retina is a highly metabolically active tissue with high-level consumption of nutrients and oxygen. This high metabolic demand requires a properly developed and maintained vascular system. The retina is nourished by two systems: the central retinal artery that supplies the inner retina and the choriocapillaris that supplies the outer retina and retinal pigment epithelium (RPE). Pathological neovascularization, characterized by endothelial cell proliferation and new vessel formation, is a common hallmark in several retinal degenerative diseases, including age-related macular degeneration (AMD). A limited number of studies have suggested that microglia, the resident immune cells of the retina, have an important role not only in the pathology but also in the formation and physiology of the retinal vascular system. Here, we review the current knowledge on microglial interaction with the retinal vascular system under physiological and pathological conditions. To do so, we first highlight the role of microglial cells in the formation and maintenance of the retinal vasculature system. Thereafter, we discuss the molecular signaling mechanisms through which microglial cells contribute to the alterations in retinal and choroidal vasculatures and to the neovascularization in AMD.

scholarly journals Choriocapillaris Loss in Advanced Age-Related Macular Degeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Carlos A. Moreira-Neto ◽  
Eric M. Moult ◽  
James G. Fujimoto ◽  
Nadia K. Waheed ◽  
Daniela Ferrara
Keyword(s):  
Macular Degeneration ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Geographic Atrophy ◽  
Age Related Macular Degeneration ◽  
Advanced Age ◽  
Tissue Loss ◽  
Age Related

The purpose of this review is to summarize the current knowledge on choriocapillaris loss in advanced age macular degeneration (AMD). Several histopathological studies in animal models and human eyes had showed that the choriocapillaris density decreases with age. However, the role of choriocapillaris loss is still unclear in AMD and its advanced forms, either choroidal neovascularization (CNV) or geographic atrophy (GA). Some authors have hypothesized that choriocapillaris loss might precede overt retinal pigment epithelium atrophy. Others have hypothesized that deposition of complement complexes on and around the choriocapillaris could be related to the tissue loss observed in early AMD. The development of imaging modalities, such as optical coherence tomography angiography (OCTA), have led to a better understanding of underlying physiopathological mechanisms in AMD. OCTA showed atrophy of choriocapillaris underneath and beyond the region of photoreceptors and RPE loss, in agreement with previous histopathologic studies. The evolution of OCTA technology suggests that CNV seems to originate from regions of severe choriocapillaris alteration. Significant progress has been made in the understanding of development and progression of GA and CNV. In vivo investigation of the choriocapillaris using OCTA may lead to new insights related to underlying disease mechanisms in AMD.

scholarly journals Retinal Pigment Epithelium Tears: Risk Factors, Mechanism and Therapeutic Monitoring

2015 ◽  
Vol 235 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Christoph R. Clemens ◽  
Nicole Eter
Keyword(s):  
Retinal Pigment Epithelium ◽  
Current Knowledge ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Therapeutic Monitoring ◽  
Temporal Association ◽  
Anti Vegf ◽  
Age Related ◽  
Rpe Tear

Tears of the retinal pigment epithelium (RPE) are most commonly associated with vascularised RPE detachment due to age-related macular degeneration (AMD), and they usually involve a deleterious loss in visual acuity. Recent studies suggest an increase in RPE tear incidences since the introduction of anti-vascular endothelial growth factor (anti-VEGF) therapies as well as a temporal association between the tear event and the intravitreal injection. As the number of AMD patients and the number of administered anti-VEGF injections increase, both the challenge of RPE tear prevention and the treatment after RPE tear formation have become more important. At the same time, the evolution of retinal imaging has significantly contributed to a better understanding of RPE tear development in recent years. This review summarises the current knowledge on RPE tear development, predictive factors, and treatment strategies before and after RPE tear formation.

scholarly journals The Role of MicroRNAs in Mitochondria-Mediated Eye Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Sabrina Carrella ◽  
Filomena Massa ◽  
Alessia Indrieri
Keyword(s):  
Current Knowledge ◽  
Expression Profiles ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
High Energy ◽  
Light Signal ◽  
Eye Diseases ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Mitochondrial Functions

The retina is among the most metabolically active tissues with high-energy demands. The peculiar distribution of mitochondria in cells of retinal layers is necessary to assure the appropriate energy supply for the transmission of the light signal. Photoreceptor cells (PRs), retinal pigment epithelium (RPE), and retinal ganglion cells (RGCs) present a great concentration of mitochondria, which makes them particularly sensitive to mitochondrial dysfunction. To date, visual loss has been extensively correlated to defective mitochondrial functions. Many mitochondrial diseases (MDs) show indeed neuro-ophthalmic manifestations, including retinal and optic nerve phenotypes. Moreover, abnormal mitochondrial functions are frequently found in the most common retinal pathologies, i.e., glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR), that share clinical similarities with the hereditary primary MDs. MicroRNAs (miRNAs) are established as key regulators of several developmental, physiological, and pathological processes. Dysregulated miRNA expression profiles in retinal degeneration models and in patients underline the potentiality of miRNA modulation as a possible gene/mutation-independent strategy in retinal diseases and highlight their promising role as disease predictive or prognostic biomarkers. In this review, we will summarize the current knowledge about the participation of miRNAs in both rare and common mitochondria-mediated eye diseases. Definitely, given the involvement of miRNAs in retina pathologies and therapy as well as their use as molecular biomarkers, they represent a determining target for clinical applications.

scholarly journals Ocular Stem Cells to Treat Retinal and Corneal Disorders

2018 ◽  
Vol 5 (1) ◽  
pp. 31-46 ◽  
Author(s):  
Biswa P. Chatterji ◽  
Godiwala Mehvash ◽  
Sunder Roma
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Therapy ◽  
Stem Cell Therapy ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Vision Impairment ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Limbal Stem Cell

Background:According to WHO, 285 million people are visually impaired out of which, 39 million are classified as blind and the remaining 246 million people have low vision which comprises of moderate vision impairment and severe vision impairment. Therapies to treat major disorders leading to visual impairment like Age-related Macular Degeneration (AMD), Stargardt’s Disease (STGD), Retinitis Pigmentosa (RP) and corneal scarring are required.In the last decade, many advances have been made to treat these disorders using stem cell therapy. For corneal damage by accidental burns, scarring or limbal stem cell deficiencies which can lead to partial or total blindness, are treated with a risky intervention like keratoplasty. To overcome issues like graft rejection caused by keratoplasty as well as have a better outcome, limbal stem cell therapy has been introduced. Similarly, Retinal Pigment Epithelium (RPE) is a supporting tissue essential in nutrient transport, production of growth factors, phagocytosis of the photoreceptors and retinol cycling.Discussion and Conlusion:Degeneration of this monolayer causes many diseases that have no prevailing treatment; however, research is being carried out to replace this simple epithelial monolayer primarily with an autologous source of cells and currently using stem cells. This review discusses the advances made in the field of ocular stem cell therapy with regards to development, cultivation and novel methods used to deliver these cells to replace the corneal and retinal epithelium as a new standard for treatment.

scholarly journals Complement System in Pathogenesis of AMD: Dual Player in Degeneration and Protection of Retinal Tissue

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Milosz P. Kawa ◽  
Anna Machalinska ◽  
Dorota Roginska ◽  
Boguslaw Machalinski
Keyword(s):  
Complement System ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Complement Components ◽  
Retinal Tissue ◽  
Age Related ◽  
Cellular Debris ◽  
Active Complement

Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly, especially in Western countries. Although the prevalence, risk factors, and clinical course of the disease are well described, its pathogenesis is not entirely elucidated. AMD is associated with a variety of biochemical abnormalities, including complement components deposition in the retinal pigment epithelium-Bruch’s membrane-choriocapillaris complex. Although the complement system (CS) is increasingly recognized as mediating important roles in retinal biology, its particular role in AMD pathogenesis has not been precisely defined. Unrestricted activation of the CS following injury may directly damage retinal tissue and recruit immune cells to the vicinity of active complement cascades, therefore detrimentally causing bystander damage to surrounding cells and tissues. On the other hand, recent evidence supports the notion that an active complement pathway is a necessity for the normal maintenance of the neurosensory retina. In this scenario, complement activation appears to have beneficial effect as it promotes cell survival and tissue remodeling by facilitating the rapid removal of dying cells and resulting cellular debris, thus demonstrating anti-inflammatory and neuroprotective activities. In this review, we discuss both the beneficial and detrimental roles of CS in degenerative retina, focusing on the diverse aspects of CS functions that may promote or inhibit macular disease.

scholarly journals A G-Protein Coupled Receptor and Macular Degeneration

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 910
Author(s):  
Anna G. Figueroa ◽  
Brian S. McKay
Keyword(s):  
Macular Degeneration ◽  
G Protein ◽  
Racial Bias ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
G Protein Coupled Receptor ◽  
Primary Defect ◽  
Age Related ◽  
G Protein Coupled

Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the world. The risk of AMD increases with age and is most common among the white population. Here, we discuss the convergence of factors related to race, pigmentation, and susceptibility to AMD, where the primary defect occurs in retinal support cells, the retinal pigment epithelium (RPE). We explore whether the observed racial bias in AMD incidence is related to innate differences in the basal level of pigmentation between races, and whether the pigmentation pathway activity in the RPE might protect from retinal degeneration. More specifically, we explore whether the downstream signaling activity of GPR143, a G-protein coupled receptor in the pigmentation pathway, might underly the racial bias of AMD and be a target to prevent the disease. Lastly, we summarize the past findings of a large retrospective study that investigated the relationship between the stimulation of GPR143 with L-DOPA, the pigmentation pathway, and AMD, to potentially help develop new ways to prevent or treat AMD. The reader of this review will come to understand the racial bias of AMD, which is related to the function of the RPE.

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