Design of Experiments for Exposure of Astrocytes to Elevated Hydrostatic Pressure and Hypoxia

2008 ◽  
Author(s):  
Shadi Rajabi ◽  
Craig A. Simmons ◽  
C. Ross Ethier
Keyword(s):  
Intraocular Pressure ◽  
Visual Field ◽  
Retinal Ganglion Cells ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Visual Field Loss ◽  
Retinal Ganglion ◽  
Common Cause ◽  
Elevated Intraocular Pressure

Glaucoma, a chronic optic neuropathy, is the second most common cause of blindness, affecting 67 million people worldwide. The damage in glaucoma occurs at the optic nerve head (ONH), where the axons of the retinal ganglion cells leave the eye posteriorly. Glaucoma is frequently associated with elevated intraocular pressure (IOP), and visual field loss can be prevented by significant lowering of IOP. Hence, the role of pressure in glaucoma is important. Unfortunately, the mechanism by which pressure leads to vision loss in glaucoma is very poorly understood.

scholarly journals Hop flower extracts mitigate retinal ganglion cell degeneration in a glaucoma mouse model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tomoko Hasegawa ◽  
Hanako O. Ikeda ◽  
Sachiko Iwai ◽  
Norio Sasaoka ◽  
Akira Kakizuka ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Visual Field ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Amyloid Β ◽  
Visual Field Loss ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Novel Therapeutic

AbstractIn glaucoma, retinal ganglion cells degenerate progressively, leading to visual field loss and blindness. Presently, the only treatment strategy for glaucoma is lowering the intraocular pressure. However, there are cases in which patients develop progressive visual field loss even though their intraocular pressures are within normal ranges. Therefore, the development of novel therapeutic strategies is an urgent endeavor. Besides high intraocular pressure, several other factors have been proposed to be associated with glaucoma progression, e.g., myopia, blood flow impairment, and amyloid β accumulation. We have previously reported that hop flower extracts possess γ-secretase inhibitory activities and reduce amyloid β deposition in the brains of Alzheimer’s disease model mice. In the current study, we showed that administration of hop flower extracts to glutamate-aspartate transporter (GLAST) knockout mice, the glaucoma model mice, attenuated glaucomatous retinal ganglion cell degeneration. Preservation of retinal ganglion cells in hop flower extract-administered mice was confirmed using optical coherence tomography, confocal scanning laser ophthalmoscopy, and retinal flatmount and histological evaluations. Hop flower extracts are, therefore, deemed a possible candidate as a novel therapeutic agent to treat glaucoma.

scholarly journals Corrigendum to “Effects of elevated intraocular pressure on mouse retinal ganglion cells” [Vision Res. 45 (2004) 169–179]

2015 ◽  
Vol 117 ◽  
pp. 136
Author(s):  
Jianzhong Ji ◽  
Peter Chang ◽  
Mark E. Pennesi ◽  
Zhuo Yang ◽  
Jian Zhang ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Elevated Intraocular Pressure

scholarly journals Glial Cells in Glaucoma: Friends, Foes, and Potential Therapeutic Targets

2021 ◽  
Vol 12 ◽  
Author(s):  
Mariana Y. García-Bermúdez ◽  
Kristine K. Freude ◽  
Zaynab A. Mouhammad ◽  
Peter van Wijngaarden ◽  
Keith K. Martin ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Glial Cells ◽  
Ganglion Cells ◽  
Treatment Strategies ◽  
Visual Field Loss ◽  
Retinal Ganglion ◽  
Therapeutic Approaches ◽  
Pressure Lowering ◽  
Underlying Pathophysiology

Glaucoma is the second leading cause of blindness worldwide, affecting ~80 million people by 2020 (1, 2). The condition is characterized by a progressive loss of retinal ganglion cells (RGCs) and their axons accompanied by visual field loss. The underlying pathophysiology of glaucoma remains elusive. Glaucoma is recognized as a multifactorial disease, and lowering intraocular pressure (IOP) is the only treatment that has been shown to slow the progression of the condition. However, a significant number of glaucoma patients continue to go blind despite intraocular pressure-lowering treatment (2). Thus, the need for alternative treatment strategies is indisputable. Accumulating evidence suggests that glial cells play a significant role in supporting RGC function and that glial dysfunction may contribute to optic nerve disease. Here, we review recent advances in understanding the role of glial cells in the pathophysiology of glaucoma. A particular focus is on the dynamic and essential interactions between glial cells and RGCs and potential therapeutic approaches to glaucoma by targeting glial cells.

scholarly journals Dual SMAD inhibition and Wnt inhibition enable efficient and reproducible differentiations of induced pluripotent stem cells into retinal ganglion cells

2019 ◽  
Author(s):  
Venkata R. M. Chavali ◽  
Naqi Haider ◽  
Sonika Rathi ◽  
Vrathasha Vrathasha ◽  
Teja Alapati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Optic Nerve ◽  
Visual Field ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Visual Field Loss ◽  
Nerve Degeneration ◽  
Retinal Ganglion

AbstractGlaucoma is a group of progressive optic neuropathies that share common biological and clinical characteristics including irreversible changes to the optic nerve and visual field loss caused by death of retinal ganglion cells (RGCs). The loss of RGCs manifests as characteristic cupping or optic nerve degeneration, resulting in visual field loss in patients with Glaucoma. Published studies on in vitro RGC differentiation from stem cells utilized classical RGC signaling pathways mimicking retinal development in vivo. Although many strategies allowed for the generation of RGCs, increased variability between experiments and lower yield hampered the cross comparison between individual lines and between experiments. To address this critical need, we developed a reproducible chemically defined in vitro methodology for generating retinal progenitor cell (RPC) populations from iPSCs, that are efficiently directed towards RGC lineage. Using this method, we reproducibly differentiated iPSCs into RGCs with greater than 80% purity, without any genetic modifications. We used small molecules and peptide modulators to inhibit BMP, TGF-β (SMAD), and canonical Wnt pathways that reduced variability between iPSC lines and yielded functional and mature iPSC-RGCs. Using CD90.2 antibody and Magnetic Activated Cell Sorter (MACS) technique, we successfully purified Thy-1 positive RGCs with nearly 95% purity.

Gene Therapy Strategies for Glaucomatous Neurodegeneration

2021 ◽  
Vol 21 ◽  
Author(s):  
Rafael Lani-Louzada ◽  
Mariana Santana Dias ◽  
Rafael Linden ◽  
Vinicius de Toledo Ribas ◽  
Hilda Petrs-Silva
Keyword(s):  
Gene Therapy ◽  
Intraocular Pressure ◽  
Retinal Ganglion Cells ◽  
Viral Vectors ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Experimental Studies ◽  
Current Treatment ◽  
Experimental Models ◽  
Retinal Ganglion

: Glaucoma leads to irreversible vision loss and current therapeutic strategies are often insufficient to prevent the progression of the disease and consequent blindness. Elevated intraocular pressure is an important risk factor, but not required for the progression of glaucomatous neurodegeneration. The demise of retinal ganglion cells represents the final common pathway of glaucomatous vision loss. Still, lifelong control of intraocular pressure is the only current treatment to prevent severe vision loss, although it frequently fails despite best practices. This scenario calls for the development of neuroprotective and pro-regenerative therapies targeting the retinal ganglion cells as well as the optic nerve. Several experimental studies have shown the potential of gene modulation as a tool for neuroprotection and regeneration. In this context, gene therapy represents an attractive approach as persistent treatment for glaucoma. Viral vectors engineered to promote overexpression of a broad range of cellular factors have been shown to protect retinal ganglion cells and/or promote axonal regeneration in experimental models. Here, we review the mechanisms involved in glaucomatous neurodegeneration and regeneration in the central nervous system. Then, we point out current limitations of gene therapy platforms and review a myriad of studies that use viral vectors to manipulate genes in retinal ganglion cells, as a strategy to promote neuroprotection and regeneration. Finally, we address the potential of combining neuroprotective and regenerative gene therapies as an approach to glaucomatous neurodegeneration.

Glaucoma management in the era of artificial intelligence

2019 ◽  
Vol 104 (3) ◽  
pp. 301-311 ◽  
Author(s):  
Sripad Krishna Devalla ◽  
Zhang Liang ◽  
Tan Hung Pham ◽  
Craig Boote ◽  
Nicholas G Strouthidis ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Deep Learning ◽  
Retinal Ganglion Cells ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Irreversible Damage ◽  
Diagnosis And Prognosis ◽  
Disease Prognosis

Glaucoma is a result of irreversible damage to the retinal ganglion cells. While an early intervention could minimise the risk of vision loss in glaucoma, its asymptomatic nature makes it difficult to diagnose until a late stage. The diagnosis of glaucoma is a complicated and expensive effort that is heavily dependent on the experience and expertise of a clinician. The application of artificial intelligence (AI) algorithms in ophthalmology has improved our understanding of many retinal, macular, choroidal and corneal pathologies. With the advent of deep learning, a number of tools for the classification, segmentation and enhancement of ocular images have been developed. Over the years, several AI techniques have been proposed to help detect glaucoma by analysis of functional and/or structural evaluations of the eye. Moreover, the use of AI has also been explored to improve the reliability of ascribing disease prognosis. This review summarises the role of AI in the diagnosis and prognosis of glaucoma, discusses the advantages and challenges of using AI systems in clinics and predicts likely areas of future progress.

scholarly journals Oral administration of a dual ETA/ETB receptor antagonist promotes neuroprotection in a rodent model of glaucoma

2020 ◽  
Author(s):  
Nolan R. McGrady ◽  
Dorota L. Stankowska ◽  
Hayden B. Jefferies ◽  
Raghu R. Krishnamoorthy
Keyword(s):  
Intraocular Pressure ◽  
Oral Administration ◽  
Receptor Antagonist ◽  
Ocular Hypertension ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Brown Norway ◽  
Retinal Ganglion ◽  
Elevated Intraocular Pressure ◽  
Iop Elevation

AbstractPurposeGlaucoma is a neurodegenerative disease associated with elevated intraocular pressure and characterized by optic nerve axonal degeneration, cupping of the optic disc and loss of retinal ganglion cells (RGCs). The endothelin (ET) system of vasoactive peptides (ET-1, ET-2, ET-3) and their G-protein coupled receptors (ETA and ETB receptors) have been shown to be contributors to the pathophysiology of glaucoma. The purpose of this study was to determine if administration of the endothelin receptor antagonist, macitentan, after the onset of IOP elevation, was neuroprotective to retinal ganglion cells in ocular hypertensive rats.MethodsBrown Norway rats were subjected to the Morrison model of ocular hypertension by injection of hypertonic saline through episcleral veins. Macitentan (5 and 10 mg/kg body wt/day) was administered orally following the elevation of IOP and rats with IOP elevation were maintained for 4 weeks. RGC function was determined by pattern electroretinography at 2 and 4 weeks post IOP elevation. Rats were euthanized by approved humane methods and retinal flat-mounts generated were immunostained with RGC-selective markers RBPMS and Brn3a. RGC counts were conducted in a masked manner.ResultsA significant protection of retinal ganglion cells against cell loss was found following oral administration of macitentan (5 and 10 mg/kg body wt/day) in rats with elevated intraocular pressure. In addition, treatment with macitentan was able to preserve RGC function as measured by pattern ERG analysis.ConclusionsMacitentan was able to promote neuroprotection independent of IOP-lowering suggesting that this could complement existing treatments to prevent neurodegeneration during ocular hypertension. The findings presented have implications for the use of macitentan as an oral formulation to promote neuroprotection in glaucoma patients.

scholarly journals Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3158
Author(s):  
Annagrazia Adornetto ◽  
Laura Rombolà ◽  
Luigi Antonio Morrone ◽  
Carlo Nucci ◽  
Maria Tiziana Corasaniti ◽  
...  
Keyword(s):  
Natural Products ◽  
Risk Factor ◽  
Intraocular Pressure ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Retinal Ganglion ◽  
Main Risk Factor ◽  
Number Of Patients ◽  
Elevated Intraocular Pressure ◽  
Underlying Mechanisms

Glaucoma, a leading cause of irreversible blindness worldwide, is an optic neuropathy characterized by the progressive death of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is recognized as the main risk factor. Despite effective IOP-lowering therapies, the disease progresses in a significant number of patients. Therefore, alternative IOP-independent strategies aiming at halting or delaying RGC degeneration is the current therapeutic challenge for glaucoma management. Here, we review the literature on the neuroprotective activities, and the underlying mechanisms, of natural compounds and dietary supplements in experimental and clinical glaucoma.

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