Cell-based therapy for ocular disorders: A promising frontier

2021 ◽  
Vol 16 ◽  
Author(s):  
Milad Ahani-Nahayati ◽  
Vahid Niazi ◽  
Alireza Moradi ◽  
Bahareh Pourjabbar ◽  
Reza Roozafzoon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wide Spectrum ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Ocular Tissue ◽  
Ocular Diseases ◽  
Cell Based Therapy ◽  
Age Related ◽  
Ocular Disorders

: As the ocular disorders causing long-term blindness or optical abnormalities of the ocular tissue affect the quality of life of patients to a large extent, awareness of their corresponding pathogenesis and the earlier detection and treatment need more consideration. Though current therapeutics result in desirable outcomes, they do not offer an inclusive solution for development of visual impairment to blindness. Accordingly, stem cells, because of their particular competencies, have gained extensive attention for application in regenerative medicine of ocular diseases. In the last decades, a wide spectrum of stem cells surrounding mesenchymal stem/stromal cells (MSC), neural stem cells (NSCs), and embryonic/induced pluripotent stem cells (ESCs/iPSCs) accompanied by Müller glia, ciliary epithelia-derived stem cells, and retinal pigment epithelial (RPE) stem cells have been widely investigated to report their safety and efficacy in preclinical models and also human subjects. In this regard, in the first interventions, RPE cell suspensions were successfully utilized to ameliorate visual defects of the patients suffering from age-related macular degeneration (AMD) after subretinal transplantation. Herein, we will explain the pathogenesis of ocular diseases and highlight the novel discoveries and recent findings in the context of stem cell-based therapies in these disorders, focusing on the in vivo reports published during the last decade.

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 Non-medical treatment for late age-related macular degeneration

2021 ◽  
Vol 21 (4) ◽  
pp. 215-219
Author(s):  
A.K. Drakon ◽  
◽  
A.G. Kurguzova ◽  
V.M. Sheludchenko ◽  
N.B. Korchazhkina ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Medical Treatment ◽  
Macular Degeneration ◽  
Retinal Pigment ◽  
Embryonic Stem ◽  
Age Related Macular Degeneration ◽  
Target Cells ◽  
Specific Gene ◽  
Age Related

Age-related macular degeneration (AMD) is the leading cause of blindness in people over 55 in developed countries. Moreover, the number of these patients will increase growth as life expectancy increases. It is estimated that late AMD accounts for half of blindness and low vision cases in European countries. A myriad of studies is currently underway to discover cutting-edge, effective therapeutic modalities. Gene therapy is a novel alternative to regular intravitreal injections of anti-VEGF agents for late wet AMD. This technique’s heart is a specific gene delivery to target cells to generate natural VEGF inhibitors. Gene therapy affecting the complement system to deactivate its end product, the membrane attack complex, is reasonable in late atrophic AMD. Studies on stem cell therapy for late atrophic AMD undergo as well. It was demonstrated that retinal pigment epithelium (RPE) cells derived from human embryonic stem cells or induced pluripotent stem cells express typical RPE markers that can phagocytize photoreceptor segments. Electrical stimulation and magnet therapy are already introduced into clinical practice to rehabilitate patients with late AMD. Magnetic and electrical fields improve impulse transmitting, activate intracellular and tissue regeneration of the retina. Recent findings are promising but require further in-depth studies. Keywords: age-related macular degeneration, retinal scar, gene therapy, stem cells, physiotherapy, rehabilitative medicine. For citation: Drakon A.K., Kurguzova A.G., Sheludchenko V.M., Korchazhkina N.B. Non-medical treatment for late age-related macular degeneration. Russian Journal of Clinical Ophthalmology. 2021;21(4):215–219 (in Russ.). DOI: 10.32364/2311-7729-2021-21-4-215-219.

scholarly journals Saffron (Crocus sativus L.) in Ocular Diseases: A Narrative Review of the Existing Evidence from Clinical Studies

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 649 ◽  
Author(s):  
Rebekka Heitmar ◽  
James Brown ◽  
Ioannis Kyrou
Keyword(s):  
Clinical Studies ◽  
Wide Spectrum ◽  
Narrative Review ◽  
Age Related Macular Degeneration ◽  
Crocus Sativus ◽  
Ocular Diseases ◽  
Neuroprotective Effects ◽  
Age Related ◽  
Underlying Mechanisms ◽  
Crocus Sativus L

Saffron (Crocus sativus L.) and its main constituents, i.e., crocin and crocetin, are natural carotenoid compounds, which have been reported to possess a wide spectrum of properties and induce pleiotropic anti-inflammatory, anti-oxidative, and neuroprotective effects. An increasing number of experimental, animal, and human studies have investigated the effects and mechanistic pathways of these compounds in order to assess their potential therapeutic use in ocular diseases (e.g., in age related macular degeneration, glaucoma, and diabetic maculopathy). This narrative review presents the key findings of published clinical studies that examined the effects of saffron and/or its constituents in the context of ocular disease, as well as an overview of the proposed underlying mechanisms mediating these effects.

Bruch’s membrane pathology: A mechanistic perspective

2020 ◽  
Vol 30 (6) ◽  
pp. 1195-1206 ◽  
Author(s):  
Aishwarya Murali ◽  
Subramanian Krishnakumar ◽  
Anuradha Subramanian ◽  
Sowmya Parameswaran
Keyword(s):  
Extracellular Matrix ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Vital Role ◽  
Age Related Macular Degeneration ◽  
Ocular Diseases ◽  
Bruch's Membrane ◽  
Bruch’S Membrane ◽  
Age Related

Bruch’s membrane, an extracellular matrix located between the retinal pigment epithelium and the choroid, plays a vital role as structural and functional support to the retinal pigment epithelium. Dysfunction of Bruch’s membrane in both age-related macular degeneration and other ocular diseases is caused mostly by extracellular matrix degeneration, deposit formation, and angiogenesis. Although these factors are dealt in greater detail with respect to the cells that are degenerated such as the retinal pigment epithelium and the endothelial cells, the pathology involving the Bruch’s membrane is often underrated. Since in most of the macular degenerations early degenerative changes are also observed in the Bruch’s membrane, addressing only the cellular component without the underlying membrane will not yield an ideal clinical benefit. This review aims to discuss the factors and the mechanisms affecting the integrity of the Bruch’s membrane, which would aid in developing an effective therapy for these pathologies.

scholarly journals A Role for PPAR in Ocular Angiogenesis

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
David Bishop-Bailey
Keyword(s):  
Age Related Macular Degeneration ◽  
Western World ◽  
Central Component ◽  
Ocular Angiogenesis ◽  
Age Related ◽  
Ocular Disorders ◽  
Common Causes ◽  
Ppar Ligands

The uses of highly selective PPAR ligands and PPAR knockout mice have shown a direct ability of PPAR to regulate angiogenesis in vitro and in vivo in animal models. PPAR ligands induce the proangiogenic growth factor VEGF in many cells and tissues, though its actions in the eye are not known. However, virtually, all tissue components of the eye express PPAR. Both angiogenesis and in particular VEGF are not only critical for the development of the retina, but they are also a central component in many common pathologies of the eye, including diabetic retinopathy and age-related macular degeneration, the most common causes of blindness in the Western world. This review, therefore, will discuss the recent evidence of PPAR-mediated angiogenesis and VEGF release in the context of ocular disorders.

scholarly journals Human iPS cell derived RPE strips for secure delivery of graft cells at a target place with minimal surgical invasion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mitsuhiro Nishida ◽  
Yuji Tanaka ◽  
Yo Tanaka ◽  
Satoshi Amaya ◽  
Nobuyuki Tanaka ◽  
...  
Keyword(s):  
Target Location ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Sheet ◽  
Invasive Procedure ◽  
Age Related Macular Degeneration ◽  
Target Area ◽  
Ips Cell ◽  
Age Related

AbstractSeveral clinical studies have been conducted into the practicality and safety of regenerative therapy using hESC/iPSC-retinal pigment epithelium (RPE) as a treatment for the diseases including age-related macular degeneration. These studies used either suspensions of RPE cells or an RPE cell sheet. The cells can be injected using a minimally invasive procedure but the delivery of an intended number of cells at an exact target location is difficult; cell sheets take a longer time to prepare, and the surgical procedure is invasive but can be placed at the target area. In the research reported here, we combined the advantages of the two approaches by producing a quickly formed hiPSC-RPE strip in as short as 2 days. The strip readily expanded into a monolayer sheet on the plate, and after transplantation in nude rats, it showed a potency to partly expand with the correct apical/basal polarity in vivo, although limited in expansion area in the presence of healthy host RPE. The strip could be injected into a target area in animal eyes using a 24G canula tip.

scholarly journals Age-Related Macular Degeneration Revisited: From Pathology and Cellular Stress to Potential Therapies

2021 ◽  
Vol 8 ◽  
Author(s):  
Majda Hadziahmetovic ◽  
Goldis Malek
Keyword(s):  
Macular Degeneration ◽  
Vision Loss ◽  
Clinical Care ◽  
Retinal Pigment ◽  
Retinal Pigment Epithelial Cells ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
The Impact

Age-related macular degeneration (AMD) is a neurodegenerative disease of the aging retina, in which patients experience severe vision loss. Therapies available to patients are limited and are only effective in a sub-population of patients. Future comprehensive clinical care depends on identifying new therapeutic targets and adopting a multi-therapeutic approach. With this goal in mind, this review examines the fundamental concepts underlying the development and progression of AMD and re-evaluates the pathogenic pathways associated with the disease, focusing on the impact of injury at the cellular level, with the understanding that critical assessment of the literature may help pave the way to identifying disease-relevant targets. During this process, we elaborate on responses of AMD vulnerable cells, including photoreceptors, retinal pigment epithelial cells, microglia, and choroidal endothelial cells, based on in vitro and in vivo studies, to select stressful agents, and discuss current therapeutic developments in the field, targeting different aspects of AMD pathobiology.

scholarly journals Stem cell-based technologies in treatment of age-related macular degeneration patients: current state of the problem

2020 ◽  
Vol 12 (4) ◽  
pp. 35-41
Author(s):  
Kirill Yu. Gayduk ◽  
Sergey V. Churashov ◽  
Alexey N. Kulikov
Keyword(s):  
Stem Cells ◽  
Macular Degeneration ◽  
Cultured Cells ◽  
Therapeutic Potential ◽  
Retinal Pigment ◽  
Antiangiogenic Therapy ◽  
Age Related Macular Degeneration ◽  
Common Disease ◽  
Treatment Methods ◽  
Age Related

Age-related macular degeneration (AMD) is the most common disease of the macula the area responsible for central vision. With regard to the pathogenesis of AMD, the main focus of most researchers is on the pathological processes occurring in the retinal pigment epithelium (RPE), which is considered as the main target of the disease. For the treatment of the dry form of the disease, which accounts for about 90% of all AMD cases, up to now no effective treatment methods were elaborated, while in the therapy of the wet form, antiangiogenic therapy, photodynamic therapy, and surgical treatment methods have been used with concrete success. Stem cells, possessing enormous therapeutic potential, are gradually being introduced into medical technologies, including ophthalmology. A number of pre-clinical studies have proven the safety of using cultured cells of the RPE, which gave rise to the beginning of clinical trials of the use of stem cells in the treatment of AMD patients. The review analyzes the data of scientific literature on the current understanding of the pathogenesis of AMD, pathogenetically substantiated therapies, including those using cell-based technologies, prospects and problems of using stem cells in the treatment of AMD patients.

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