<p>Regeneration of trabecular meshwork in primary open angle glaucoma by stem cell therapy: a new treatment approach</p>

AbstractWe previously identified and characterized human trabecular meshwork stem cells (TMSCs) based on high expression of ABCG2/p75 positivity and high nucleus to cytoplasmic ratio. These TMSCs expressing high ABCG2 and p75 were located to the insert region of the human TM. Additionally, we demonstrated an age-related reduction in the TMSC content which was significantly associated with TM cell loss. In continuation, this study was aimed to determine the TMSC content in glaucomatous donor eyes wherein a drastic reduction in TM cellularity has already been reported. Anterior segments from known glaucomatous (n = 6) and age-matched normal (n = 8) donors were dissected into four quadrants. A minimum of three sections from each quadrant were used for histopathological analysis as well as immunostaining. Analysis of hematoxylin and eosin-stained sections from glaucomatous tissues revealed a decrease in total TM cellularity, thickening of trabecular beams, fusion of trabeculae, absence of patent Schlemm’s canal compared to age-matched controls. In addition, the TM thickness at various positions of the meshwork and the coronal as well as the meridional diameters of the Schlemm’s canal were observed to be significantly reduced in glaucomatous eyes. Further, sections from both the groups were immunostained for universal stem cell marker ABCG2 and neural crest derived stem cell marker p75. The images were acquired using Leica SP8 confocal microscope. Quantification of total TM cellularity based on nuclear counterstain (mean ± SD) using ImageJ identified 69.33 ± 12.77 cells/section in control eyes. In glaucomatous donors, the TM cellularity was found to be reduced significantly to 41.83 ± 9.0 (p = 0.0007). In addition, a reduction in the percentage of TMSCs (cells with high ABCG2 expression and p75 positivity) was evident in glaucomatous donors (0.14 ± 0.17%) compared to age-matched controls (4.73 ± 5.46%) (p = 0.064). Thus, the present study confirmed the significant decline in TM cellularity and a reducing trend in the TMSC content, though this reduction was non-significant in glaucomatous donor eyes. Further studies are essential to elucidate the role of TMSCs in the pathogenesis of primary open angle glaucoma.

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Schlemm’s Canal and Trabecular Meshwork in Eyes with Primary Open Angle Glaucoma: A Comparative Study Using High-Frequency Ultrasound Biomicroscopy

PLoS ONE ◽

10.1371/journal.pone.0145824 ◽

2016 ◽

Vol 11 (1) ◽

pp. e0145824 ◽

Cited By ~ 27

Author(s):

Xiaoqin Yan ◽

Mu Li ◽

Zhiqi Chen ◽

Ying Zhu ◽

Yinwei Song ◽

...

Keyword(s):

Comparative Study ◽

Trabecular Meshwork ◽

High Frequency ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Ultrasound Biomicroscopy ◽

Open Angle ◽

High Frequency Ultrasound ◽

Schlemm's Canal ◽

Frequency Ultrasound

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Evolving Concepts for Use of Stem Cells and Tissue Engineering for Cardiac Regeneration

Advances in Medical Technologies and Clinical Practice - Optimizing Assistive Technologies for Aging Populations ◽

10.4018/978-1-4666-9530-6.ch011 ◽

2016 ◽

pp. 279-313

Author(s):

Jahnavi Sarvepalli ◽

Rajalakshmi Santhakumar ◽

Rama Shanker Verma

Keyword(s):

Tissue Engineering ◽

Stem Cell ◽

Cell Therapy ◽

Stem Cell Therapy ◽

Treatment Options ◽

Treatment Strategies ◽

Basic Research ◽

Underlying Mechanism ◽

Repair Mechanisms ◽

New Treatment

The incidence of cardiovascular disease (CVD) in adults are increasing worldwide with impaired repair mechanisms, leading to tissue and organ failure. With the current advancements, life expectancy has improved and has led to search for new treatment strategies that improves tissue regeneration. Recently, stem cell therapy and tissue engineering has captured the attention of clinicians, scientists, and patients as alternative treatment options. The overall clinical experience of these suggests that they can be safely used in the right clinical setting. Ultimately, large outcome trials will have to be conducted to assess their efficacy. Clinical trials have to be carefully designed and patient safety must remain the key concern. At the same time, continued basic research is required to understand the underlying mechanism of cell-based therapies and cell tissue interactions. This chapter reviews the evolving paradigm of stem cell therapy and tissue engineering approaches for clinical application and explores its implications.

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Neuroinflammation in Primary Open-Angle Glaucoma

Journal of Clinical Medicine ◽

10.3390/jcm9103172 ◽

2020 ◽

Vol 9 (10) ◽

pp. 3172 ◽

Cited By ~ 1

Author(s):

Stefania Vernazza ◽

Sara Tirendi ◽

Anna Maria Bassi ◽

Carlo Enrico Traverso ◽

Sergio Claudio Saccà

Keyword(s):

Oxidative Stress ◽

Immune Response ◽

Trabecular Meshwork ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

Glaucoma Surgery ◽

Open Angle ◽

Antioxidant Defences ◽

Age Related ◽

Wide Range

Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increasing evidence suggests oxidative damage and immune response defects are key factors contributing to glaucoma onset. Indeed, both the failure of the trabecular meshwork tissue in the conventional outflow pathway and the neuroinflammation process, which drives the neurodegeneration, seem to be linked to the age-related over-production of free radicals (i.e., mitochondrial dysfunction) and to oxidative stress-linked immunostimulatory signaling. Several previous studies have described a wide range of oxidative stress-related makers which are found in glaucomatous patients, including low levels of antioxidant defences, dysfunction/activation of glial cells, the activation of the NF-κB pathway and the up-regulation of pro-inflammatory cytokines, and so on. However, the intraocular pressure is still currently the only risk factor modifiable by medication or glaucoma surgery. This present review aims to summarize the multiple cellular processes, which promote different risk factors in glaucoma including aging, oxidative stress, trabecular meshwork defects, glial activation response, neurodegenerative insults, and the altered regulation of immune response.

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Role of Fibronectin in Primary Open Angle Glaucoma

Cells ◽

10.3390/cells8121518 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1518 ◽

Cited By ~ 6

Author(s):

Jennifer A. Faralli ◽

Mark S. Filla ◽

Donna M. Peters

Keyword(s):

United States ◽

Trabecular Meshwork ◽

Vision Loss ◽

Primary Open Angle Glaucoma ◽

Open Angle Glaucoma ◽

The United States ◽

Open Angle ◽

Cell Matrix ◽

Fibronectin Fibrils

Primary open angle glaucoma (POAG) is the most common form of glaucoma and the 2nd most common cause of irreversible vision loss in the United States. Nearly 67 million people have the disease worldwide including >3 million in the United States. A major risk factor for POAG is an elevation in intraocular pressure (IOP). The increase in IOP is believed to be caused by an increase in the deposition of extracellular matrix proteins, in particular fibronectin, in a region of the eye known as the trabecular meshwork (TM). How fibronectin contributes to the increase in IOP is not well understood. The increased density of fibronectin fibrils is thought to increase IOP by altering the compliance of the trabecular meshwork. Recent studies, however, also suggest that the composition and organization of fibronectin fibrils would affect IOP by changing the cell-matrix signaling events that control the functional properties of the cells in the trabecular meshwork. In this article, we will discuss how changes in the properties of fibronectin and fibronectin fibrils could contribute to the regulation of IOP.

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Comparing Medium-Term Clinical Outcomes following XEN® 45 and XEN® 63 Device Implantation

Journal of Ophthalmology ◽

10.1155/2020/4796548 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Aitor Fernández-García ◽

Ying Zhou ◽

Mercedes García-Alonso ◽

Henry D. Andrango ◽

Francisco Poyales ◽

...

Keyword(s):

Observational Study ◽

Clinical Outcomes ◽

Surgical Procedures ◽

Primary Open Angle Glaucoma ◽

Treatment Approach ◽

Open Angle Glaucoma ◽

Open Angle ◽

Medium Term ◽

Device Implantation ◽

The Mean

Purpose. To evaluate medium-term clinical outcomes with XEN® 45 or XEN® 63 Gel Stent (Allergan, Dublin, Ireland) for treatment of primary open angle glaucoma (POAG). Materials and Methods. Retrospective, descriptive, and observational study involving 40 patients implanted with a XEN® 45 Gel Stent and 34 implanted with a XEN® 63 Gel Stent who had undergone POAG surgery and had been followed up and controlled between 12 and 36 months. Results. IOP dropped from 18.02 ± 5.23 mmHg preop to 13.81 ± 1.88, 14.80 ± 2.23, and 14.62 ± 1.90 at 1, 2, and 3 years after surgery (p<0.001) consecutively with XEN® 45 and from 19.00 ± 6.11 mmHg preop to 15.47 ± 2.45, 14.66 ± 2.45, and 15.46 ± 2.48 at 1, 2, and 3 years after surgery (p<0.001) with XEN® 63. The number of drugs used by patients to treat their glaucoma decreased after undergoing surgery in both groups. Within the XEN® 45 group, mean changes at 1 year, 2 years, and 3 years amounted to 70%, 74.3%, and 37.5%, respectively, whereas within the XEN® 63 group, the mean reduction was 75%, 79.8%, and 71.9%. When comparing the outcomes for two groups, the differences did not prove to be statistically significant. More than 90% of the procedures included in the study (using either gel-stent device) were completed without any noteworthy complications. Conclusion. POAG surgical procedures with either XEN® 45 or XEN® 63 Gel Stent implantation could be a safe and effective treatment approach.

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