scholarly journals Perspectives of Stem Cell-Based Therapy for Age-Related Retinal Degenerative Diseases

2017 ◽  
Author(s):  
Vladimir Holan ◽  
Barbora Hermankova ◽  
Jan Kossl
Keyword(s):  
Stem Cell ◽  
Degenerative Diseases ◽  
Cell Based Therapy ◽  
Age Related ◽  
Retinal Degenerative Diseases

scholarly journals Perspectives of Stem Cell–Based Therapy for Age-Related Retinal Degenerative Diseases

2017 ◽  
Vol 26 (9) ◽  
pp. 1538-1541 ◽  
Author(s):  
Vladimir Holan ◽  
Barbora Hermankova ◽  
Jan Kossl
Keyword(s):  
Stem Cell ◽  
Treatment Protocol ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
Cell Type ◽  
Retinal Cells ◽  
Cell Based Therapy ◽  
Age Related ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases, which include age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and glaucoma, mostly affect the elderly population and are the most common cause of decreased quality of vision or even blindness. So far, there is no satisfactory treatment protocol to prevent, stop, or cure these disorders. A great hope and promise for patients suffering from retinal diseases is represented by stem cell–based therapy that could replace diseased or missing retinal cells and support regeneration. In this respect, mesenchymal stem cells (MSCs) that can be obtained from the particular patient and used as autologous cells have turned out to be a promising stem cell type for treatment. Here we show that MSCs can differentiate into cells expressing markers of retinal cells, inhibit production of pro-inflammatory cytokines by retinal tissue, and produce a number of growth and neuroprotective factors for retinal regeneration. All of these properties make MSCs a prospective cell type for cell-based therapy of age-related retinal degenerative diseases.

scholarly journals Mesenchymal Stem Cell-Based Therapy for Retinal Degenerative Diseases: Experimental Models and Clinical Trials

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 588
Author(s):  
Vladimir Holan ◽  
Katerina Palacka ◽  
Barbora Hermankova
Keyword(s):  
Clinical Trials ◽  
Experimental Studies ◽  
Experimental Models ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
Retinal Cells ◽  
Cell Based Therapy ◽  
Age Related ◽  
Retinal Degenerative Diseases

Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy or glaucoma, represent the main causes of a decreased quality of vision or even blindness worldwide. However, despite considerable efforts, the treatment possibilities for these disorders remain very limited. A perspective is offered by cell therapy using mesenchymal stem cells (MSCs). These cells can be obtained from the bone marrow or adipose tissue of a particular patient, expanded in vitro and used as the autologous cells. MSCs possess potent immunoregulatory properties and can inhibit a harmful inflammatory reaction in the diseased retina. By the production of numerous growth and neurotrophic factors, they support the survival and growth of retinal cells. In addition, MSCs can protect retinal cells by antiapoptotic properties and could contribute to the regeneration of the diseased retina by their ability to differentiate into various cell types, including the cells of the retina. All of these properties indicate the potential of MSCs for the therapy of diseased retinas. This view is supported by the recent results of numerous experimental studies in different preclinical models. Here we provide an overview of the therapeutic properties of MSCs, and their use in experimental models of retinal diseases and in clinical trials.

Gene and Induced Pluripotent Stem Cell Therapy for Retinal Diseases

2019 ◽  
Vol 20 (1) ◽  
pp. 201-216 ◽  
Author(s):  
Akiko Maeda ◽  
Michiko Mandai ◽  
Masayo Takahashi
Keyword(s):  
Stem Cell ◽  
Retinitis Pigmentosa ◽  
Visual Information ◽  
Pluripotent Stem Cell ◽  
Induced Pluripotent Stem Cell ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
Age Related ◽  
Retinal Degenerative Diseases ◽  
Induced Pluripotent

Given the importance of visual information to many daily activities, retinal degenerative diseases—which include both inherited conditions (such as retinitis pigmentosa) and acquired conditions (such as age-related macular degeneration)—can have a dramatic impact on human lives. The therapeutic options for these diseases remain limited. Since the discovery of the first causal gene for retinitis pigmentosa almost three decades ago, more than 250 genes have been identified, and gene therapies have been rapidly developed. Simultaneously, stem cell technologies such as induced pluripotent stem cell–based transplantation have advanced and have been applied to the treatment of retinal degenerative diseases. Here, we review recent progress in these expanding fields and discuss the potential for precision medicine in ophthalmic care.

scholarly journals Human Stem Cell Transplantation for Retinal Degenerative Diseases. Where Are We Now?

Medicina ◽  
2022 ◽  
Vol 58 (1) ◽  
pp. 102
Author(s):  
Ignacio Alcalde ◽  
Cristina Sánchez-Fernández ◽  
Carla Martín ◽  
Nagore De Pablo ◽  
Nahla Jemni-Damer ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Age Related Macular Degeneration ◽  
Retinal Diseases ◽  
Degenerative Diseases ◽  
Age Related ◽  
Retinal Degenerative Diseases

Background and Objectives: Irreversible visual impairment is mainly caused by retinal degenerative diseases such as age-related macular degeneration and retinitis pigmentosa. Stem cell research has experienced rapid progress in recent years, and researchers and clinical ophthalmologists are trying to implement this promising technology to treat retinal degeneration. The objective of this systematic review is to analyze currently available data from clinical trials applying stem cells to treat human retinal diseases. Materials and Methods: We performed a systematic literature search in PubMed to identify articles related with stem cell therapies to retinal diseases published prior to September 2021. Furthermore, a systematic search in ClinicalTrials (NIH U.S. National Library of Medicine) was performed to identify clinical trials using stem cells to treat retinal diseases. A descriptive analysis of status, conditions, phases, interventions, and outcomes is presented here. Conclusions: To date, no available therapy based on stem cell transplantation is approved for use with patients. However, numerous clinical trials are currently finishing their initial phases and, in general, the outcomes related to implantation techniques and their long-term safety seem promising. In the next few years, we expect to see quantifiable results pertaining to visual function improvement.

scholarly journals Resveratrol Modulates SIRT1 and DNMT Functions and Restores LINE-1 Methylation Levels in ARPE-19 Cells under Oxidative Stress and Inflammation

2018 ◽  
Vol 19 (7) ◽  
pp. 2118 ◽  
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Maria Mazzone ◽  
Francesco Giuliano ◽  
Guido Basile ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment ◽  
Sirtuin 1 ◽  
Age Related Macular Degeneration ◽  
Degenerative Diseases ◽  
P Values ◽  
Sirt1 Expression ◽  
Inflammatory Conditions ◽  
Age Related ◽  
Retinal Degenerative Diseases

The role of epigenetic alterations in the pathogenesis of retinal degenerative diseases, including age-related macular degeneration (AMD), has been pending so far. Our study investigated the effect of oxidative stress and inflammation on DNA methyltransferases (DNMTs) and Sirtuin 1 (SIRT1) functions, as well as on long interspersed nuclear element-1 (LINE-1) methylation, in human retinal pigment epithelial (ARPE-19) cells. Therefore, we evaluated whether treatment with resveratrol may modulate DNMT and SIRT1 functions and restore changes in LINE-1 methylation. Cells were treated with 25 mU/mL glucose oxidase (GOx) or 10 µg/mL lipopolysaccharide (LPS) to mimic oxidative or inflammatory conditions, respectively. Oxidative stress decreased DNMT1, DNMT3a, DNMT3b, and SIRT1 expression (p-values < 0.05), as well as total DNMTs (−28.5%; p < 0.0001) and SIRT1 (−29.0%; p < 0.0001) activities. Similarly, inflammatory condition decreased DNMT1 and SIRT1 expression (p-values < 0.05), as well as total DNMTs (−14.9%; p = 0.007) and SIRT1 (−20.1%; p < 0.002) activities. Interestingly, GOx- and LPS-treated cells exhibited lower LINE-1 methylation compared to controls (p-values < 0.001). We also demonstrated that treatment with 10 μM resveratrol for 24 h counteracted the detrimental effect on DNMT and SIRT1 functions, and LINE-1 methylation, in cells under oxidative and inflammatory conditions. However, further studies should explore the perspectives of resveratrol as a suitable strategy for the prevention and/or treatment of retinal degenerative diseases.

scholarly journals Autophagy activated via GRP78 to alleviate endoplasmic reticulum stress for cell survival in blue light-mediated damage of A2E-laden RPEs

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jingyang Feng ◽  
Yuhong Chen ◽  
Bing Lu ◽  
Xiangjun Sun ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Signaling Pathway ◽  
Blue Light ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Degenerative Diseases ◽  
Caspase 12 ◽  
Age Related ◽  
Retinal Degenerative Diseases

Abstract Background Retinal pigment epithelium cells (RPEs) are critical for maintaining retinal homeostasis. Accumulation of age-related lipofuscin, N-retinylidene-N-retinylethanolamine (A2E), makes RPEs vulnerable to blue light-mediated damage, which represents an initial cause of some retinal degenerative diseases. This study investigated the activation of autophagy and the signaling pathway involved in glucose-related protein 78 (GRP78) induced autophagy in blue light-mediated damage of A2E-laden RPEs. In addition, we explored whether autophagy could play a protective role by alleviating endoplasmic reticulum (ER) stress to promote RPEs survival. Methods RPEs were incubated with 25 μM A2E for 2 h and exposed to blue light for 20 min. The expression of ER stress-related apoptotic proteins, CHOP and caspase-12, as well as autophagy marker LC3 were measured by western blot analysis. Autophagosomes were observed by both transmission electron microscopy and immunofluorescence assays. GRP78 interference performed by short hairpin RNA (shRNA) was used to identify the signaling pathway involved in GRP78 induced autophagy. Cell death was assessed using TUNEL analysis. Results Treatment with A2E and blue light markedly increased the expression of ER stress-related apoptotic molecules CHOP and caspase-12. The activation of autophagy was recognized by observing autophagosomes at ultrastructural level. Additionally, punctate distributions of LC3 immunofluorescence and enhanced conversions of LC3-I to LC3-II were found in A2E and blue light-treated RPEs. Moreover, GRP78 interference reduced AMPK phosphorylation and promoted mTOR activity, thereby downregulating autophagy. In addition, the inhibition of autophagy made RPEs vulnerable to A2E and blue light damage. In contrast, the autophagy inducer rapamycin alleviated ER stress to promote RPEs survival. Conclusions GRP78 activates autophagy via AMPK/mTOR in blue light-mediated damage of A2E-laden RPEs in vitro. Autophagy may be a vital endogenous cytoprotective process to alleviate stress for RPEs survival in retinal degenerative diseases.

scholarly journals Mechanisms and Treatment of Light-Induced Retinal Degeneration-Associated Inflammation: Insights from Biochemical Profiling of the Aqueous Humor

2020 ◽  
Vol 21 (3) ◽  
pp. 704 ◽  
Author(s):  
Dmitry V. Chistyakov ◽  
Viktoriia E. Baksheeva ◽  
Veronika V. Tiulina ◽  
Sergei V. Goriainov ◽  
Nadezhda V. Azbukina ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Degeneration ◽  
Aqueous Humor ◽  
Rabbit Model ◽  
Age Related Macular Degeneration ◽  
Protective Effects ◽  
Cyclooxygenase Inhibitor ◽  
Degenerative Diseases ◽  
Age Related ◽  
Retinal Degenerative Diseases

Ocular inflammation contributes to the pathogenesis of blind-causing retinal degenerative diseases, such as age-related macular degeneration (AMD) or photic maculopathy. Here, we report on inflammatory mechanisms that are associated with retinal degeneration induced by bright visible light, which were revealed while using a rabbit model. Histologically and electrophysiologically noticeable degeneration of the retina is preceded and accompanied by oxidative stress and inflammation, as evidenced by granulocyte infiltration and edema in this tissue, as well as the upregulation of total protein, pro-inflammatory cytokines, and oxidative stress markers in aqueous humor (AH). Consistently, quantitative lipidomic studies of AH elucidated increase in the concentration of arachidonic (AA) and docosahexaenoic (DHA) acids and lyso-platelet activating factor (lyso-PAF), together with pronounced oxidative and inflammatory alterations in content of lipid mediators oxylipins. These alterations include long-term elevation of prostaglandins, which are synthesized from AA via cyclooxygenase-dependent pathways, as well as a short burst of linoleic acid derivatives that can be produced by both enzymatic and non-enzymatic free radical-dependent mechanisms. The upregulation of all oxylipins is inhibited by the premedication of the eyes while using mitochondria-targeted antioxidant SkQ1, whereas the accumulation of prostaglandins and lyso-PAF can be specifically suppressed by topical treatment with cyclooxygenase inhibitor Nepafenac. Interestingly, the most prominent antioxidant and anti-inflammatory benefits and overall retinal protective effects are achieved by simultaneous administrating of both drugs indicating their synergistic action. Taken together, these findings provide a rationale for using a combination of mitochondria-targeted antioxidant and cyclooxygenase inhibitor for the treatment of inflammatory components of retinal degenerative diseases.

scholarly journals The Diverse Roles of TIMP-3: Insights into Degenerative Diseases of the Senescent Retina and Brain

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 39 ◽  
Author(s):  
Dewing ◽  
Carare ◽  
Lotery ◽  
Ratnayaka
Keyword(s):  
Stem Cell ◽  
Age Related Macular Degeneration ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Degenerative Diseases ◽  
Risk Alleles ◽  
Age Related ◽  
New Treatments ◽  
Extracellular Environment ◽  
Age Related Changes

Tissue inhibitor of metalloproteinase-3 (TIMP-3) is a component of the extracellular environment, where it mediates diverse processes including matrix regulation/turnover, inflammation and angiogenesis. Rare TIMP-3 risk alleles and mutations are directly linked with retinopathies such as age-related macular degeneration (AMD) and Sorsby fundus dystrophy, and potentially, through indirect mechanisms, with Alzheimer’s disease. Insights into TIMP-3 activities may be gleaned from studying Sorsby-linked mutations. However, recent findings do not fully support the prevailing hypothesis that a gain of function through the dimerisation of mutated TIMP-3 is responsible for retinopathy. Findings from Alzheimer’s patients suggest a hitherto poorly studied relationship between TIMP-3 and the Alzheimer’s-linked amyloid-beta (A) proteins that warrant further scrutiny. This may also have implications for understanding AMD as aged/diseased retinae contain high levels of A. Findings from TIMP-3 knockout and mutant knock-in mice have not led to new treatments, particularly as the latter does not satisfactorily recapitulate the Sorsby phenotype. However, recent advances in stem cell and in vitro approaches offer novel insights into understanding TIMP-3 pathology in the retina-brain axis, which has so far not been collectively examined. We propose that TIMP-3 activities could extend beyond its hitherto supposed functions to cause age-related changes and disease in these organs.

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