Journal of Clinical Medicine

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16 pages, 3198 KiB

Open AccessArticle

Cathepsin B Localizes in the Caveolae and Participates in the Proteolytic Cascade in Trabecular Meshwork Cells. Potential New Drug Target for the Treatment of Glaucoma

by April Nettesheim, Myoung Sup Shim, Angela Dixon, Urmimala Raychaudhuri, Haiyan Gong and Paloma B. Liton

J. Clin. Med. 2021, 10(1), 78; https://doi.org/10.3390/jcm10010078 - 28 Dec 2020

Cited by 16 | Viewed by 2960

Abstract

Extracellular matrix (ECM) deposition in the trabecular meshwork (TM) is one of the hallmarks of glaucoma, a group of human diseases and leading cause of permanent blindness. The molecular mechanisms underlying ECM deposition in the glaucomatous TM are not known, but it is [...] Read more.

Extracellular matrix (ECM) deposition in the trabecular meshwork (TM) is one of the hallmarks of glaucoma, a group of human diseases and leading cause of permanent blindness. The molecular mechanisms underlying ECM deposition in the glaucomatous TM are not known, but it is presumed to be a consequence of excessive synthesis of ECM components, decreased proteolytic degradation, or both. Targeting ECM deposition might represent a therapeutic approach to restore outflow facility in glaucoma. Previous work conducted in our laboratory identified the lysosomal enzyme cathepsin B (CTSB) to be expressed on the cellular surface and to be secreted into the culture media in trabecular meshwork (TM) cells. Here, we further investigated the role of CTSB on ECM remodeling and outflow physiology in vitro and in CSTB^ko mice. Our results indicate that CTSB localizes in the caveolae and participates in the pericellular degradation of ECM in TM cells. We also report here a novel role of CTSB in regulating the expression of PAI-1 and TGFβ/Smad signaling in TM cells vitro and in vivo in CTSB^ko mice. We propose enhancing CTSB activity as a novel therapeutic target to attenuate fibrosis and ECM deposition in the glaucomatous outflow pathway. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

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14 pages, 1970 KiB

Open AccessArticle

Intra-Cellular Calcium Signaling Pathways (PKC, RAS/RAF/MAPK, PI3K) in Lamina Cribrosa Cells in Glaucoma

by Mustapha Irnaten, Aisling Duff, Abbot Clark and Colm O’Brien

J. Clin. Med. 2021, 10(1), 62; https://doi.org/10.3390/jcm10010062 - 26 Dec 2020

Cited by 15 | Viewed by 2801

Abstract

The lamina cribrosa (LC) is a key site of fibrotic damage in glaucomatous optic neuropathy and the precise mechanisms of LC change remain unclear. Elevated Ca²⁺ is a major driver of fibrosis, and therefore intracellular Ca²⁺ signaling pathways are relevant glaucoma-related [...] Read more.

The lamina cribrosa (LC) is a key site of fibrotic damage in glaucomatous optic neuropathy and the precise mechanisms of LC change remain unclear. Elevated Ca²⁺ is a major driver of fibrosis, and therefore intracellular Ca²⁺ signaling pathways are relevant glaucoma-related mechanisms that need to be studied. Protein kinase C (PKC), mitogen-activated MAPK kinases (p38 and p42/44-MAPK), and the PI3K/mTOR axis are key Ca²⁺ signal transducers in fibrosis and we therefore investigated their expression and activity in normal and glaucoma cultured LC cells. We show, using Western immune-blotting, that hyposmotic-induced cellular swelling activates PKCα, p42/p44, and p38 MAPKs, the activity is transient and biphasic as it peaks between 2 min and 10 min. The expression and activity of PKCα, p38 and p42/p44-MAPKs are significantly (p < 0.05) increased in glaucoma LC cells at basal level, and at different time-points after hyposmotic stretch. We also found elevated mRNA expression of mRNA expression of PI3K, IP3R, mTOR, and CaMKII in glaucoma LC cells. This study has identified abnormalities in multiple calcium signaling pathways (PKCα, MAPK, PI3K) in glaucoma LC cells, which might have significant functional and therapeutic implications in optic nerve head (ONH) fibrosis and cupping in glaucoma. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

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9 pages, 2675 KiB

Open AccessArticle

Canaloplasty in Pigmentary Glaucoma: Long-Term Outcomes and Proposal of a New Hypothesis on Its Intraocular Pressure Lowering Mechanism

by Paolo Brusini and Veronica Papa

J. Clin. Med. 2020, 9(12), 4024; https://doi.org/10.3390/jcm9124024 - 12 Dec 2020

Cited by 3 | Viewed by 2535

Abstract

This study presents the long-term results on canaloplasty in a group of patients affected by pigmentary glaucoma, and studies the progression of the disease after surgery. Material and methods: Twenty-nine eyes of 25 patients with pigmentary glaucoma in maximum tolerated medical therapy with [...] Read more.

This study presents the long-term results on canaloplasty in a group of patients affected by pigmentary glaucoma, and studies the progression of the disease after surgery. Material and methods: Twenty-nine eyes of 25 patients with pigmentary glaucoma in maximum tolerated medical therapy with significant visual field damage progression underwent canaloplasty and were followed up to 11 years (mean 59.8 ± 30.1 months). All patients underwent a complete ophthalmic examination every 6 months. Results: The pre-operative mean intraocular pressure (IOP) was 31.8 mmHg ± 10.9 (range 21–70) with an average of 3.3 medications. After 1, 2, 3, and 4 years, the mean IOP was 15.9 ± 4.0, 14.4 ± 7.3, 14.1 ± 2.1, and 15.7 mmHg, respectively, with 0.4, 0.5, and 0.7 medications, respectively. Four patients underwent trabeculectomy after 3 to 30 months due to uncontrolled IOP. Gonioscopy showed a significant reduction of pigment in trabecular meshwork in all cases, starting from the sixth month. In some cases, the pigment was almost completely reabsorbed after two years, suggesting an accelerated transit and escape of the granules through the trabecular spaces. Conclusions: Canaloplasty seems to be a reasonable option in treating patients affected by progressive pigmentary glaucoma. The reabsorption of pigment granules from the trabecular meshwork could, at least in part, explain the relatively high success rate observed after this surgical procedure. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

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14 pages, 1874 KiB

Open AccessArticle

Can Polyphenols in Eye Drops Be Useful for Trabecular Protection from Oxidative Damage?

by Sergio Claudio Saccà, Alberto Izzotti, Stefania Vernazza, Sara Tirendi, Sonia Scarfì, Stefano Gandolfi and Anna Maria Bassi

J. Clin. Med. 2020, 9(11), 3584; https://doi.org/10.3390/jcm9113584 - 6 Nov 2020

Cited by 7 | Viewed by 1934

Abstract

Polyphenols, with anti-oxidant properties, counteract oxidative stress effects. Increasing evidence has found oxidative stressto be the main risk factor for trabecular meshwork (TM) damage, leading to high-tension glaucoma. Topical anti-oxidants could represent a new target for glaucoma treatment. Our aim is to investigate [...] Read more.

Polyphenols, with anti-oxidant properties, counteract oxidative stress effects. Increasing evidence has found oxidative stressto be the main risk factor for trabecular meshwork (TM) damage, leading to high-tension glaucoma. Topical anti-oxidants could represent a new target for glaucoma treatment. Our aim is to investigate the protective mechanisms on a human TM culture of a patented polyphenol and fatty acid (iTRAB^®)formulation in response to oxidative stress using an advanced invitromodel consisting of 3D-human TM cells, embedded in a natural hydrogel, and a milli-scaled multi-organ device model for constantdynamic conditions. The 3D-human TM cells(3D-HTMCs) were treated daily with 500 µM H₂O₂or 500 µM H₂O₂and 0.15% iTRAB^®(m/v) for 72 h, and molecular differences in the intracellular reactive oxygen species (iROS), state of the cells, activation of the apoptosis pathway and NF-kB and the expression ofinflammatory and fibrotic markers wereanalyzed at different time-points.Concomitant exposure significantly reduced iROS and restored TM viability, iTRAB^® having a significant inhibitory effect on the apoptotic pathway, activation of NF-κB, induction of pro-inflammatory (IL-1α, IL-1ß and TNFα) and pro-fibrotic (TGFβ) cytokines and the matrix metalloproteinase expressions. It is clear that this specific anti-oxidant provides a valid TM protection, suggesting iTRAB^® could be an adjuvant therapy in primary open-angle glaucoma (POAG). Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

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15 pages, 3714 KiB

Open AccessArticle

Effects of Netarsudil on Actin-Driven Cellular Functions in Normal and Glaucomatous Trabecular Meshwork Cells: A Live Imaging Study

by Kate E. Keller and Casey Kopczynski

J. Clin. Med. 2020, 9(11), 3524; https://doi.org/10.3390/jcm9113524 - 31 Oct 2020

Cited by 8 | Viewed by 2701

Abstract

The actin cytoskeleton of trabecular meshwork (TM) cells is a therapeutic target for lowering intraocular pressure (IOP) in glaucoma patients. Netarsudil (the active ingredient in Rhopressa^TM) is a Rho-associated protein kinase inhibitor that induces disassembly of actin stress fibers. Here, we [...] Read more.

The actin cytoskeleton of trabecular meshwork (TM) cells is a therapeutic target for lowering intraocular pressure (IOP) in glaucoma patients. Netarsudil (the active ingredient in Rhopressa^TM) is a Rho-associated protein kinase inhibitor that induces disassembly of actin stress fibers. Here, we used live cell imaging of SiR-actin-labeled normal (NTM) and glaucomatous TM (GTM) cells to investigate actin dynamics during actin-driven biological processes with and without netarsudil treatment. Actin stress fibers were thicker in GTM than NTM cells and took longer (>120 min) to disassemble following addition of 1 µM netarsudil. Actin-rich extracellular vesicles (EVs) were derived by two mechanisms: exocytosis of intracellular-derived vesicles, and cleavage of filopodial tips, which detached the filopodia from the substratum, allowing them to retract to the cell body. While some phagocytosis was noted in untreated TM cells, netarsudil potently stimulated phagocytic uptake of EVs. Netarsudil treatment induced lateral fusion of tunneling nanotubes (TNTs) that connected adjacent TM cells; TNTs are important for TM cellular communication. Together, our results suggest that netarsudil may clear outflow channels in TM tissue by inducing phagocytosis and/or by modulating TM communication via EVs and TNTs. These cellular functions likely work together to regulate IOP in normal and glaucomatous TM. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

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13 pages, 3551 KiB

Open AccessArticle

Diffusional Kurtosis Imaging of White Matter Degeneration in Glaucoma

by Carlo Nucci, Francesco Garaci, Simone Altobelli, Francesco Di Ciò, Alessio Martucci, Francesco Aiello, Simona Lanzafame, Francesca Di Giuliano, Eliseo Picchi, Silvia Minosse, Massimo Cesareo, Maria Giovanna Guerrisi, Roberto Floris, Luca Passamonti and Nicola Toschi

J. Clin. Med. 2020, 9(10), 3122; https://doi.org/10.3390/jcm9103122 - 27 Sep 2020

Cited by 21 | Viewed by 2760

Abstract

Glaucoma is an optic neuropathy characterized by death of retinal ganglion cells and loss of their axons, progressively leading to blindness. Recently, glaucoma has been conceptualized as a more diffuse neurodegenerative disorder involving the optic nerve and also the entire brain. Consistently, previous [...] Read more.

Glaucoma is an optic neuropathy characterized by death of retinal ganglion cells and loss of their axons, progressively leading to blindness. Recently, glaucoma has been conceptualized as a more diffuse neurodegenerative disorder involving the optic nerve and also the entire brain. Consistently, previous studies have used a variety of magnetic resonance imaging (MRI) techniques and described widespread changes in the grey and white matter of patients. Diffusion kurtosis imaging (DKI) provides additional information as compared with diffusion tensor imaging (DTI), and consistently provides higher sensitivity to early microstructural white matter modification. In this study, we employ DKI to evaluate differences among healthy controls and a mixed population of primary open angle glaucoma patients ranging from stage I to V according to Hodapp–Parrish–Anderson visual field impairment classification. To this end, a cohort of patients affected by primary open angle glaucoma (n = 23) and a group of healthy volunteers (n = 15) were prospectively enrolled and underwent an ophthalmological evaluation followed by magnetic resonance imaging (MRI) using a 3T MR scanner. After estimating both DTI indices, whole-brain, voxel-wise statistical comparisons were performed in white matter using Tract-Based Spatial Statistics (TBSS). We found widespread differences in several white matter tracts in patients with glaucoma relative to controls in several metrics (mean kurtosis, kurtosis anisotropy, radial kurtosis, and fractional anisotropy) which involved localization well beyond the visual pathways, and involved cognitive, motor, face recognition, and orientation functions amongst others. Our findings lend further support to a causal brain involvement in glaucoma and offer alternative explanations for a number of multidomain impairments often observed in glaucoma patients. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

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0 pages, 2918 KiB

Open AccessArticle

Computational Analysis of Clinical and Molecular Markers and New Theranostic Possibilities in Primary Open-Angle Glaucoma

by María D. Pinazo-Durán, José J. García-Medina, José M. Bolarín, Silvia M. Sanz-González, Mar Valero-Vello, Javier Abellán-Abenza, Vicente Zanón-Moreno and Javier Moreno-Montañés

J. Clin. Med. 2020, 9(9), 3032; https://doi.org/10.3390/jcm9093032 - 21 Sep 2020

Cited by 4 | Viewed by 2493

Abstract

Primary open-angle glaucoma (POAG) is a paramount cause of irreversible visual disability worldwide. We focus on identifying clinical and molecular facts that may help elucidating the pathogenic mechanisms of the disease. By using ophthalmological approaches (biomicroscopy, ocular fundus, optical coherence tomography, and perimetry) [...] Read more.

Primary open-angle glaucoma (POAG) is a paramount cause of irreversible visual disability worldwide. We focus on identifying clinical and molecular facts that may help elucidating the pathogenic mechanisms of the disease. By using ophthalmological approaches (biomicroscopy, ocular fundus, optical coherence tomography, and perimetry) and experimental tests (enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC), and Western blot/immunoblotting) directed to evaluate the oxidative stress, inflammation, apoptosis, and neurodegeneration processes, we gather information to build a network of data to perform a computational bioinformatics analysis. Our results showed strong interaction of the above players and its downstream effectors in POAG pathogenesis. In conclusion, specific risk factors were identified, and molecules involved in multiple pathways were found in relation to anterior and posterior eye segment glaucoma changes, pointing to new theranostic challenges for better managing POAG progression. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

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13 pages, 1755 KiB

Open AccessArticle

Volume of Lateral Geniculate Nucleus in Patients with Glaucoma in 7Tesla MRI

by Ewa Kosior-Jarecka, Anna Pankowska, Piotr Polit, Andrzej Stępniewski, Mark Roger Symms, Paulina Kozioł, Tomasz Żarnowski and Radosław Pietura

J. Clin. Med. 2020, 9(8), 2382; https://doi.org/10.3390/jcm9082382 - 26 Jul 2020

Cited by 12 | Viewed by 2402

Abstract

The aim of the study was to assess the volume of the lateral geniculate nucleus (LGN) in patients with open-angle glaucoma in 7Tesla MRI and to evaluate its relation to RNFL thickness and VF indices. Material and methods. The studied group consisted of [...] Read more.

The aim of the study was to assess the volume of the lateral geniculate nucleus (LGN) in patients with open-angle glaucoma in 7Tesla MRI and to evaluate its relation to RNFL thickness and VF indices. Material and methods. The studied group consisted of 20 open-angle glaucoma patients with bilaterally the same stage of glaucoma (11 with early glaucoma and nine with advanced glaucoma) and nine healthy volunteers from the Department of Diagnostics and Microsurgery of Glaucoma, Medical University of Lublin, Poland. Circumpapillary RNFL-thickness measurements were performed using OCT in all patients and visual fields were performed in the glaucoma group. A 7Tesla MRI was performed to assess the volume of both lateral geniculate bodies. Results. The LGN volume varied significantly between groups from 122.1 ± 14.4 mm³ (right LGN) and 101.6 ± 13.3 mm³ (left LGN) in the control group to 80.2 ± 17.7 mm³ (right LGN) and 71.8 ± 14.2 mm³ (left LGN) in the advanced glaucoma group (right LGN p = 0.003, left LGN p = 0.018). However, volume values from early glaucoma: right LGN = 120.2 ± 26.5 mm³ and left LGN = 103.2 ± 28.0 mm³ differed significantly only from values from the advanced group (right LGN p = 0.006, left LGN p = 0.012), but not from controls (right LGN p = 0.998, left LGN p = 0.986). There were no significant correlations between visual field indices (MD (mean deviation) and VFI (visual field index)) and LGN volumes in both glaucoma groups. Significant correlations between mean RNFL (retinal nerve fiber layers) thickness and corresponding and contralateral LGN were observed for the control group (corresponding LGN: p = 0.064; contralateral LGN: p = 0.031) and early glaucoma (corresponding LGN: p = 0.017; contralateral LGN: p = 0.008), but not advanced glaucoma (corresponding LGN: p = 0.496; contralateral LGN: p = 0.258). Conclusions. The LGN volume decreases in the course of glaucoma. These changes are correlated with RNFL thickness in early stages of glaucoma and are not correlated with visual field indices. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

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18 pages, 485 KiB

Open AccessArticle

Clinical-Evolutionary Staging System of Primary Open-Angle Glaucoma Using Optical Coherence Tomography

by Alfonso Parra-Blesa, Alfredo Sanchez-Alberca and Jose Javier Garcia-Medina

J. Clin. Med. 2020, 9(5), 1530; https://doi.org/10.3390/jcm9051530 - 19 May 2020

Cited by 5 | Viewed by 2787

Abstract

Background: Primary open-angle glaucoma (POAG) is considered one of the main causes of blindness. Detection of POAG at early stages and classification into evolutionary stages is crucial to blindness prevention. Methods: 1001 patients were enrolled, of whom 766 were healthy subjects and 235 [...] Read more.

Background: Primary open-angle glaucoma (POAG) is considered one of the main causes of blindness. Detection of POAG at early stages and classification into evolutionary stages is crucial to blindness prevention. Methods: 1001 patients were enrolled, of whom 766 were healthy subjects and 235 were ocular hypertensive or glaucomatous patients in different stages of the disease. Spectral domain optical coherence tomography (SD-OCT) was used to determine Bruch’s membrane opening-minimum rim width (BMO-MRW) and the thicknesses of peripapillary retinal nerve fibre layer (RNFL) rings with diameters of 3.0, 4.1 and 4.7 mm centred on the optic nerve. The BMO-MRW rim and RNFL rings were divided into seven sectors (G-T-TS-TI-N-NS-NI). The k-means algorithm and linear discriminant analysis were used to classify patients into disease stages. Results: We defined four glaucoma stages and provided a new model for classifying eyes into these stages, with an overall accuracy greater than 92% (88% when including healthy eyes). An online application was also implemented to predict the probability of glaucoma stage for any given eye. Conclusions: We propose a new objective algorithm for classifying POAG into clinical-evolutionary stages using SD-OCT. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

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13 pages, 4522 KiB

Open AccessArticle

Glaucomatous Maculopathy: Thickness Differences on Inner and Outer Macular Layers between Ocular Hypertension and Early Primary Open-Angle Glaucoma Using 8 × 8 Posterior Pole Algorithm of SD-OCT

by Jose Javier Garcia-Medina, Monica del-Rio-Vellosillo, Ana Palazon-Cabanes, Maria Dolores Pinazo-Duran, Vicente Zanon-Moreno and Maria Paz Villegas-Perez

J. Clin. Med. 2020, 9(5), 1503; https://doi.org/10.3390/jcm9051503 - 16 May 2020

Cited by 12 | Viewed by 2566

Abstract

The purpose of this study was to compare the thickness of all inner and outer macular layers between ocular hypertension (OHT) and early primary open-angle glaucoma (POAG) using spectral domain optical coherence tomography (SD-OCT) 8 × 8 posterior pole algorithm (8 × 8 [...] Read more.

The purpose of this study was to compare the thickness of all inner and outer macular layers between ocular hypertension (OHT) and early primary open-angle glaucoma (POAG) using spectral domain optical coherence tomography (SD-OCT) 8 × 8 posterior pole algorithm (8 × 8 PPA). Fifty-seven eyes of 57 OHT individuals and fifty-seven eyes of 57 early POAG patients were included. The thickness of macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform and nuclear layer, photoreceptor layer (PRL) and retinal pigment epithelium were obtained in 64 cells for each macular layer and mean thickness of superior and inferior hemispheres was also calculated. Thinning of superior and inferior hemisphere mean thickness in mRNFL, GCL and IPL and thickening of superior and inferior hemisphere mean thickness in PRL and inferior hemisphere in INL were found in early GPAA group. Otherwise, heatmaps representing cell-to-cell comparisons showed thinning patterns in inner retinal layers (except for INL) and thickening patterns in outer retinal layers in GPAA group. We found that 8 × 8 PPA not only allows the detection of significant thinning patterns in inner retinal layers, but also thickening patterns in outer retinal layers when comparing early POAG eyes to OHT eyes. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

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Review

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10 pages, 214 KiB

Open AccessReview

Pars Plana Vitrectomy and the Risk of Ocular Hypertension and Glaucoma: Where Are We?

by Tommaso Rossi and Guido Ripandelli

J. Clin. Med. 2020, 9(12), 3994; https://doi.org/10.3390/jcm9123994 - 10 Dec 2020

Cited by 12 | Viewed by 2519

Abstract

Purpose is to review the pathogenic mechanism for ocular hypertension and glaucoma development after pars plana vitrectomy. Both acute and chronic causes are considered, and special attention is paid to the theories and clinical evidence on the risk of developing Open Angle Glaucoma [...] Read more.

Purpose is to review the pathogenic mechanism for ocular hypertension and glaucoma development after pars plana vitrectomy. Both acute and chronic causes are considered, and special attention is paid to the theories and clinical evidence on the risk of developing Open Angle Glaucoma (OAG) after Pars Plana Vitrectomy (PPV). Most existing scientific literature on the issue agree on the role of ascorbate as an oxygen scavenger within the vitreous chamber. Oxygen tension in the vitreous and anterior chamber is maximum inn proximity of the retinal surface and endothelium, respectively and steeply decreases toward the lens, on both sides, and trabecular meshwork. Vitreous removal and, to a lesser extent, liquefaction, greatly reduces oxygen tension gradient in vitreous chamber while cataract extraction has similar effects on anterior chamber oxygen gradients. Oxygen derivatives originated from the cornea and retina are actively reduced by the vitreous gel and/or the crystalline lens. Vitreous removal and cataract extraction reduce drastically this function. Most reported clinical series confirm this hypothesis although protocol difference and follow-up length greatly impact the reliability of results. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

20 pages, 2111 KiB

Open AccessReview

Cannabinoids in Glaucoma Patients: The Never-Ending Story

by Andrea Passani, Chiara Posarelli, Angela Tindara Sframeli, Laura Perciballi, Marco Pellegrini, Gianluca Guidi and Michele Figus

J. Clin. Med. 2020, 9(12), 3978; https://doi.org/10.3390/jcm9123978 - 8 Dec 2020

Cited by 21 | Viewed by 5326

Abstract

Glaucoma is one of the principal causes of irreversible blindness worldwide. Yet, intraocular pressure (IOP) is the main modifiable risk factor for disease progression. In the never-ending challenge to develop new and effective drugs, several molecules have been tested as anti-glaucoma agents thanks [...] Read more.

Glaucoma is one of the principal causes of irreversible blindness worldwide. Yet, intraocular pressure (IOP) is the main modifiable risk factor for disease progression. In the never-ending challenge to develop new and effective drugs, several molecules have been tested as anti-glaucoma agents thanks to their pressure-lowering capabilities. Among these molecules, the cannabinoids have been investigated as possible anti-glaucoma drugs since the early 1970s. Cannabinoids are a large class of chemical compounds that exploit their effects by interaction with cannabinoid receptors 1 and 2. These receptors are widely expressed in the human retina where they may influence important functions such as photo-transduction, amacrine cell network maintenance, and IOP regulation. Therefore, in past years several studies have been conducted in order to assess the IOP lowering effects of cannabinoids. PRISMA guidelines have been used to perform a literature search on Pubmed and Scopus aiming to investigate the mechanism of IOP lowering effects and the potential benefits of orally administered, inhaled, topical, and intravenous cannabinoids in the treatment of glaucoma patients. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

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25 pages, 2473 KiB

Open AccessReview

Anterior Chamber Angle Assessment Techniques: A Review

by Ivano Riva, Eleonora Micheletti, Francesco Oddone, Carlo Bruttini, Silvia Montescani, Giovanni De Angelis, Luigi Rovati, Robert N. Weinreb and Luciano Quaranta

J. Clin. Med. 2020, 9(12), 3814; https://doi.org/10.3390/jcm9123814 - 25 Nov 2020

Cited by 44 | Viewed by 17405

Abstract

Assessment of the anterior chamber angle (ACA) is an essential part of the ophthalmological examination. It is intrinsically related to the diagnosis and treatment of glaucoma and has a role in its prevention. Although slit-lamp gonioscopy is considered the gold-standard technique for ACA [...] Read more.

Assessment of the anterior chamber angle (ACA) is an essential part of the ophthalmological examination. It is intrinsically related to the diagnosis and treatment of glaucoma and has a role in its prevention. Although slit-lamp gonioscopy is considered the gold-standard technique for ACA evaluation, its poor reproducibility and the long learning curve are well-known shortcomings. Several new imaging techniques for angle evaluation have been developed in the recent years. However, whether these instruments may replace or not gonioscopy in everyday clinical practice remains unclear. This review summarizes the last findings in ACA evaluation, focusing on new instruments and their application to the clinical practice. Special attention will be given to the comparison between these new techniques and traditional slit-lamp gonioscopy. Whereas ultrasound biomicroscopy and anterior segment optical coherence tomography provide quantitative measurements of the anterior segment’s structures, new gonio-photographic systems allow for a qualitative assessment of angle findings, similarly to gonioscopy. Recently developed deep learning algorithms provide an automated classification of angle images, aiding physicians in taking faster and more efficient decisions. Despite new imaging techniques made analysis of the ACA more objective and practical, the ideal method for ACA evaluation has still to be determined. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

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40 pages, 2285 KiB

Open AccessReview

Neuroinflammation in Primary Open-Angle Glaucoma

by Stefania Vernazza, Sara Tirendi, Anna Maria Bassi, Carlo Enrico Traverso and Sergio Claudio Saccà

J. Clin. Med. 2020, 9(10), 3172; https://doi.org/10.3390/jcm9103172 - 30 Sep 2020

Cited by 48 | Viewed by 4323

Abstract

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 [...] Read more.

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. Full article

(This article belongs to the Special Issue Update on Glaucoma: Pathogenesis and Treatment)

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