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Pharmaceuticals
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Pharmacology of Glaucoma
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Pharmacology of Glaucoma

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (15 July 2023) | Viewed by 19675

Special Issue Editors

Dr. Elie Beit-Yannai

E-Mail Website
Guest Editor
Clinical Biochemistry and Pharmacology Department, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel
Interests: glaucoma; signaling; extracellular vesicles; oxidative stress
Prof. Dr. Ponugoti Vasantha Rao

E-Mail Website
Guest Editor
Department of Ophthalmology, Duke University School of Medicine, Durham, NC 27710, USA
Interests: glaucoma; cataract

Special Issue Information

Dear Colleagues,

Glaucoma, an ocular condition characterized by elevated intraocular pressure (IOP), is one of the leading causes of irreversible blindness. Progressive loss of retinal ganglion cells (RGCs) and degeneration of optic nerve axons constitute the pathological hallmarks of glaucoma. IOP due to dysfunction of trabecular meshwork (TM) is considered to be a predominant risk factor for glaucoma. Currently, lowering of IOP has been demonstrated to reduce the progression of vision loss and is a mainstay of treatment for all types of glaucoma. Strategies used to lower IOP include drugs, lasers, or surgery. However, most physicians and patients use drug therapy as the first treatment strategy.

This Special Issue of the Journal of Pharmaceuticals aims to highlight recent advances in the pharmacology of current glaucoma treatments, which could contribute to the easier, safer, and more effective management of glaucoma.

Dr. Elie Beit-Yannai
Prof. Dr. Ponugoti Vasantha Rao
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • glaucoma
  • intraocular pressure
  • trabecular meshwork
  • retinal ganglion cells
  • optic nerve/optic head damage
  • medical treatment

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Published Papers (7 papers)

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Research

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12 pages, 1778 KiB  
Article
Analysis of Corticosteroid-Induced Glaucoma Using the Japanese Adverse Drug Event Reporting Database
by Ayano Kawabe and Yoshihiro Uesawa
Pharmaceuticals 2023, 16(7), 948; https://doi.org/10.3390/ph16070948 - 30 Jun 2023
Cited by 5 | Viewed by 2216
Abstract
Glaucoma is the most common cause of blindness, which significantly reduces quality of life. Most glaucoma cases are primary glaucoma; nevertheless, many patients suffer from glaucoma caused by drugs, such as corticosteroids. A comprehensive review of the risks associated with corticosteroid-induced glaucoma is [...] Read more.
Glaucoma is the most common cause of blindness, which significantly reduces quality of life. Most glaucoma cases are primary glaucoma; nevertheless, many patients suffer from glaucoma caused by drugs, such as corticosteroids. A comprehensive review of the risks associated with corticosteroid-induced glaucoma is limited. Therefore, we used the Japanese Adverse Drug Event Reporting Database (JADER) published by the Pharmaceuticals and Medical Devices Agency (PMDA) to analyze the risk factors associated with glaucoma and the trends and characteristics of corticosteroid-induced glaucoma. We did not find sex or age differences associated with the onset of glaucoma. Hierarchical clustering and principal component analysis revealed that triamcinolone acetonide and betamethasone sodium phosphate, which are used around the eyes in Japan, are more likely to induce intraocular pressure (IOP) elevation compared with other corticosteroids. Increased IOP is a direct cause of glaucoma. Based on these findings, it may be necessary to limit or avoid the use of these corticosteroids. Full article
(This article belongs to the Special Issue Pharmacology of Glaucoma)
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11 pages, 311 KiB  
Article
Use Pattern of Ophthalmic Antiglaucoma Agents with and without Preservatives: A Cross-Sectional Study
by Luis Fernando Valladales-Restrepo, María Camila Oyuela-Gutiérrez, Ana Camila Delgado-Araujo and Jorge Enrique Machado-Alba
Pharmaceuticals 2023, 16(5), 743; https://doi.org/10.3390/ph16050743 - 12 May 2023
Viewed by 1736
Abstract
Background: Different drugs have been approved to reduce the intraocular pressure. However, most of them contain preservatives to maintain sterility and these can be toxic to the ocular surface. The aim was to determine the patterns of use of antiglaucoma agents and ophthalmic [...] Read more.
Background: Different drugs have been approved to reduce the intraocular pressure. However, most of them contain preservatives to maintain sterility and these can be toxic to the ocular surface. The aim was to determine the patterns of use of antiglaucoma agents and ophthalmic preservatives in a group of patients from Colombia. Methods: A cross-sectional study that identified ophthalmic antiglaucoma agents from a population database of 9.2 million. Sociodemographic and pharmacological variables were considered. Descriptive and bivariate analyses were performed. Results: A total of 38,262 patients were identified, with a mean age of 69.2 ± 13.3 years, and 58.6% were women. A total of 98.8% were prescribed antiglaucoma drugs in multidose containers. The most widely used were prostaglandin analogs (59.9%), especially latanoprost (51.6%) and β-blockers (59.2%). A total of 54.7% of patients received combined management, especially with fixed-dose combination (FDC) drugs (41.3%). A total of 94.1% used antiglaucoma drugs with preservatives (benzalkonium chloride, 68.4%). Conclusions: The pharmacological treatment of glaucoma was very heterogeneous, but the most commonly used therapeutic groups were in accordance with the recommendations of clinical practice guidelines but with differences by sex and age. Most of the patients were exposed to preservatives, especially benzalkonium chloride, but the wide use of FDC drugs can minimize toxicity on the ocular surface. Full article
(This article belongs to the Special Issue Pharmacology of Glaucoma)
22 pages, 1960 KiB  
Article
Screening of Antiglaucoma, Antidiabetic, Anti-Alzheimer, and Antioxidant Activities of Astragalus alopecurus Pall—Analysis of Phenolics Profiles by LC-MS/MS
by Leyla Güven, Adem Erturk, Fatma Demirkaya Miloğlu, Saleh Alwasel and İlhami Gulcin
Pharmaceuticals 2023, 16(5), 659; https://doi.org/10.3390/ph16050659 - 28 Apr 2023
Cited by 29 | Viewed by 3146
Abstract
Astragalus species are traditionally used for diabetes, ulcers, leukemia, wounds, stomachaches, sore throats, abdominal pain, and toothaches. Although the preventive effects of Astragalus species against diseases are known, there is no record of the therapeutic effects of Astragalus alopecurus. In this study, [...] Read more.
Astragalus species are traditionally used for diabetes, ulcers, leukemia, wounds, stomachaches, sore throats, abdominal pain, and toothaches. Although the preventive effects of Astragalus species against diseases are known, there is no record of the therapeutic effects of Astragalus alopecurus. In this study, we aimed to evaluate the in vitro antiglaucoma, antidiabetic, anti-Alzheimer’s disease, and antioxidant activities of the methanolic (MEAA) and water (WEAA) extracts of the aerial part of A. alopecurus. Additionally, its phenolic compound profiles were analyzed by liquid chromatography–tandem mass spectrometry (LC–MS/MS). MEAA and WEAA were evaluated for their inhibition ability on α-glycosidase, α-amylase, acetylcholinesterase (AChE), and human carbonic anhydrase II (hCA II) enzymes. The phenolic compounds of MEAA were analyzed by LC-MS/MS. Furthermore, total phenolic and flavonoid contents were determined. In this context, the antioxidant activity was evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), N,N-dimethyl-p-phenylene diamine (DMPD), ferric reducing antioxidant power (FRAP), cupric ions (Cu2+) reducing antioxidant capacity (CUPRAC), ferric ions (Fe3+) reducing, and ferrous ions (Fe2+) chelating methods. MEAA and WEAA had IC50 values of 9.07 and 2.24 μg/mL for α-glycosidase, 693.15 and 346.58 μg/mL for α-amylase, 1.99 and 2.45 μg/mL for AChE, and 147.7 and 171.7 μg/mL for hCA II. While the total phenolic amounts in MEAA and WEAA were 16.00 and 18.50 μg gallic acid equivalent (GAE)/mg extract, the total flavonoid contents in both extracts were calculated as 66.23 and 33.115 μg quercetin equivalent (QE)/mg, respectively. MEAA and WEAA showed, respectively, variable activities on DPPH radical scavenging (IC50: 99.02 and 115.53 μg/mL), ABTS radical scavenging (IC50: 32.21 and 30.22 µg/mL), DMPD radical scavenging (IC50: 231.05 and 65.22 μg/mL), and Fe2+ chelating (IC50: 46.21 and 33.01 μg/mL). MEAA and WEAA reducing abilities were, respectively, Fe3+ reducing (λ700: 0.308 and 0.284), FRAP (λ593: 0.284 and 0.284), and CUPRAC (λ450: 0.163 and 0.137). A total of 35 phenolics were scanned, and 10 phenolic compounds were determined by LC-MS/MS analysis. LC-MS/MS revealed that MEAA mainly contained isorhamnetin, fumaric acid, and rosmarinic acid derivatives. This is the first report indicating that MEAA and WEAA have α-glycosidase, α-amylase, AChE, hCA II inhibition abilities, and antioxidant activities. These results demonstrate the potential of Astragalus species through antioxidant properties and enzyme inhibitor ability traditionally used in medicine. This work provides the foundation for further research into the establishment of novel therapeutics for diabetes, glaucoma, and Alzheimer’s disease. Full article
(This article belongs to the Special Issue Pharmacology of Glaucoma)
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21 pages, 5706 KiB  
Article
Azithromycin and Sildenafil May Have Protective Effects on Retinal Ganglion Cells via Different Pathways: Study in a Rodent Microbead Model
by Tal Corina Sela, Alon Zahavi, Moran Friedman-Gohas, Shirel Weiss, Amir Sternfeld, Astrid Ilguisonis, Danielle Badash, Noa Geffen, Ron Ofri, Yaniv BarKana and Nitza Goldenberg-Cohen
Pharmaceuticals 2023, 16(4), 486; https://doi.org/10.3390/ph16040486 - 24 Mar 2023
Cited by 1 | Viewed by 2228
Abstract
Decreased blood flow to the optic nerve (ON) and neuroinflammation are suggested to play an important role in the pathophysiology of glaucoma. This study investigated the potential neuroprotective effect of azithromycin, an anti-inflammatory macrolide, and sildenafil, a selective phosphodiesterase-5 inhibitor, on retinal ganglion [...] Read more.
Decreased blood flow to the optic nerve (ON) and neuroinflammation are suggested to play an important role in the pathophysiology of glaucoma. This study investigated the potential neuroprotective effect of azithromycin, an anti-inflammatory macrolide, and sildenafil, a selective phosphodiesterase-5 inhibitor, on retinal ganglion cell survival in a glaucoma model, which was induced by microbead injection into the right anterior chamber of 50 wild-type (WT) and 30 transgenic toll-like receptor 4 knockout (TLR4KO) mice. Treatment groups included intraperitoneal azithromycin 0.1 mL (1 mg/0.1 mL), intravitreal sildenafil 3 µL, or intraperitoneal sildenafil 0.1 mL (0.24 μg/3 µL). Left eyes served as controls. Microbead injection increased intraocular pressure (IOP), which peaked on day 7 in all groups and on day 14 in azithromycin-treated mice. Furthermore, the retinas and ON of microbead-injected eyes showed a trend of increased expression of inflammatory- and apoptosis-related genes, mainly in WT and to a lesser extent in TLR4KO mice. Azithromycin reduced the BAX/BCL2 ratio, TGFβ, and TNFα levels in the ON and CD45 expression in WT retina. Sildenafil activated TNFα-mediated pathways. Both azithromycin and sildenafil exerted a neuroprotective effect in WT and TLR4KO mice with microbead-induced glaucoma, albeit via different pathways, without affecting IOP. The relatively low apoptotic effect observed in microbead-injected TLR4KO mice suggests a role of inflammation in glaucomatous damage. Full article
(This article belongs to the Special Issue Pharmacology of Glaucoma)
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Review

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26 pages, 3175 KiB  
Review
Immunomodulatory and Antioxidant Drugs in Glaucoma Treatment
by Francesco Buonfiglio, Norbert Pfeiffer and Adrian Gericke
Pharmaceuticals 2023, 16(9), 1193; https://doi.org/10.3390/ph16091193 - 22 Aug 2023
Cited by 9 | Viewed by 3842
Abstract
Glaucoma, a group of diseases characterized by progressive retinal ganglion cell loss, cupping of the optic disc, and a typical pattern of visual field defects, is a leading cause of severe visual impairment and blindness worldwide. Elevated intraocular pressure (IOP) is the leading [...] Read more.
Glaucoma, a group of diseases characterized by progressive retinal ganglion cell loss, cupping of the optic disc, and a typical pattern of visual field defects, is a leading cause of severe visual impairment and blindness worldwide. Elevated intraocular pressure (IOP) is the leading risk factor for glaucoma development. However, glaucoma can also develop at normal pressure levels. An increased susceptibility of retinal ganglion cells to IOP, systemic vascular dysregulation, endothelial dysfunction, and autoimmune imbalances have been suggested as playing a role in the pathophysiology of normal-tension glaucoma. Since inflammation and oxidative stress play a role in all forms of glaucoma, the goal of this review article is to present an overview of the inflammatory and pro-oxidant mechanisms in the pathophysiology of glaucoma and to discuss immunomodulatory and antioxidant treatment approaches. Full article
(This article belongs to the Special Issue Pharmacology of Glaucoma)
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29 pages, 474 KiB  
Review
Pharmaceutical Approaches to Normal Tension Glaucoma
by Maria Letizia Salvetat, Francesco Pellegrini, Leopoldo Spadea, Carlo Salati and Marco Zeppieri
Pharmaceuticals 2023, 16(8), 1172; https://doi.org/10.3390/ph16081172 - 17 Aug 2023
Cited by 7 | Viewed by 3621
Abstract
Normal tension glaucoma (NTG) is defined as a subtype of primary open-angle glaucoma (POAG) in which the intraocular pressure (IOP) values are constantly within the statistically normal range without treatment and represents approximately the 30–40% of all glaucomatous cases. The pathophysiology of this [...] Read more.
Normal tension glaucoma (NTG) is defined as a subtype of primary open-angle glaucoma (POAG) in which the intraocular pressure (IOP) values are constantly within the statistically normal range without treatment and represents approximately the 30–40% of all glaucomatous cases. The pathophysiology of this condition is multifactorial and is still not completely well known. Several theories have been proposed to explain the onset and progression of this disease, which can be divided into IOP-dependent and IOP-independent factors, suggesting different therapeutic strategies. The current literature strongly supports the fundamental role of IOP in NTG. The gold standard treatment for NTG tends to be based on the lowering IOP even if “statistically normal”. Numerous studies have shown, however, that the IOP reduction alone is not enough to slow down or stop the disease progression in all cases, suggesting that other IOP-independent risk factors may contribute to the NTG pathogenesis. In addition to IOP-lowering strategies, several different therapeutic approaches for NTG have been proposed, based on vaso-active, antioxidant, anti-inflammatory and/or neuroprotective substances. To date, unfortunately, there are no standardized or proven treatment alternatives for NTG when compared to traditional IOP reduction treatment regimes. The efficacy of the IOP-independent strategies in decreasing the risk or treating NTG still remains inconclusive. The aim of this review is to highlight strategies reported in the current literature to treat NTG. The paper also describes the challenges in finding appropriate and pertinent treatments for this potentially vision-threatening disease. Further comprehension of NTG pathophysiology can help clinicians determine when to use IOP-lowering treatments alone and when to consider additional or alternatively individualized therapies focused on particular risk factors, on a case-by-case basis. Full article
(This article belongs to the Special Issue Pharmacology of Glaucoma)
13 pages, 786 KiB  
Review
Pharmacological Approaches to Modulate the Scarring Process after Glaucoma Surgery
by Debora Collotta, Simona Colletta, Virginia Carlucci, Claudia Fruttero, Antonio Maria Fea and Massimo Collino
Pharmaceuticals 2023, 16(6), 898; https://doi.org/10.3390/ph16060898 - 19 Jun 2023
Cited by 8 | Viewed by 2134
Abstract
Glaucoma is an acquired optic neuropathy that results in a characteristic optic nerve head appearance and visual field loss. Reducing the IOP is the only factor that can be modified, and the progression of the disease can be managed through medication, laser treatment, [...] Read more.
Glaucoma is an acquired optic neuropathy that results in a characteristic optic nerve head appearance and visual field loss. Reducing the IOP is the only factor that can be modified, and the progression of the disease can be managed through medication, laser treatment, or surgery. Filtering procedures are used when target pressure cannot be obtained with less invasive methods. Nevertheless, these procedures require accurate control of the fibrotic process, which can hamper filtration, thus, negatively affecting the surgical success. This review explores the available and potential pharmacological treatments that modulate the scarring process after glaucoma surgery, analyzing the most critical evidence available in the literature. The modulation of scarring is based on non-steroidal anti-inflammatory drugs (NSAIDs), mitomycin, and 5-fluorouracil. In the long term, the failure rate of filtering surgery is mainly due to the limitations of the current strategies caused by the complexity of the fibrotic process and the pharmacological and toxicological aspects of the drugs that are currently in use. Considering these limitations, new potential treatments were investigated. This review suggests that a better approach to tackle the fibrotic process may be to hit multiple targets, thus increasing the inhibitory potential against excessive scarring following surgery. Full article
(This article belongs to the Special Issue Pharmacology of Glaucoma)
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