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      Unveiling the role of CaMKII in retinal degeneration: from biological mechanism to therapeutic strategies

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          Abstract

          Ca 2+/calmodulin-dependent protein kinase II (CaMKII) is a family of broad substrate specificity serine (Ser)/threonine (Thr) protein kinases that play a crucial role in the Ca 2+-dependent signaling pathways. Its significance as an intracellular Ca 2+ sensor has garnered abundant research interest in the domain of neurodegeneration. Accumulating evidences suggest that CaMKII is implicated in the pathology of degenerative retinopathies such as diabetic retinopathy (DR), age-related macular degeneration (AMD), retinitis pigmentosa (RP) and glaucoma optic neuropathy. CaMKII can induce the aberrant proliferation of retinal blood vessels, influence the synaptic signaling, and exert dual effects on the survival of retinal ganglion cells and pigment epithelial cells. Researchers have put forth multiple therapeutic agents, encompassing small molecules, peptides, and nucleotides that possess the capability to modulate CaMKII activity. Due to its broad range isoforms and splice variants therapeutic strategies seek to inhibit specifically the CaMKII are confronted with considerable challenges. Therefore, it becomes crucial to discern the detrimental and advantageous aspects of CaMKII, thereby facilitating the development of efficacious treatment. In this review, we summarize recent research findings on the cellular and molecular biology of CaMKII, with special emphasis on its metabolic and regulatory mechanisms. We delve into the involvement of CaMKII in the retinal signal transduction pathways and discuss the correlation between CaMKII and calcium overload. Furthermore, we elaborate the therapeutic trials targeting CaMKII, and introduce recent developments in the zone of CaMKII inhibitors. These findings would enrich our knowledge of CaMKII, and shed light on the development of a therapeutic target for degenerative retinopathy.

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          Global Prevalence of Myopia and High Myopia and Temporal Trends from 2000 through 2050.

          Myopia is a common cause of vision loss, with uncorrected myopia the leading cause of distance vision impairment globally. Individual studies show variations in the prevalence of myopia and high myopia between regions and ethnic groups, and there continues to be uncertainty regarding increasing prevalence of myopia.
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            The pathophysiology and treatment of glaucoma: a review.

            Glaucoma is a worldwide leading cause of irreversible vision loss. Because it may be asymptomatic until a relatively late stage, diagnosis is frequently delayed. A general understanding of the disease pathophysiology, diagnosis, and treatment may assist primary care physicians in referring high-risk patients for comprehensive ophthalmologic examination and in more actively participating in the care of patients affected by this condition. To describe current evidence regarding the pathophysiology and treatment of open-angle glaucoma and angle-closure glaucoma. A literature search was conducted using MEDLINE, the Cochrane Library, and manuscript references for studies published in English between January 2000 and September 2013 on the topics open-angle glaucoma and angle-closure glaucoma. From the 4334 abstracts screened, 210 articles were selected that contained information on pathophysiology and treatment with relevance to primary care physicians. The glaucomas are a group of progressive optic neuropathies characterized by degeneration of retinal ganglion cells and resulting changes in the optic nerve head. Loss of ganglion cells is related to the level of intraocular pressure, but other factors may also play a role. Reduction of intraocular pressure is the only proven method to treat the disease. Although treatment is usually initiated with ocular hypotensive drops, laser trabeculoplasty and surgery may also be used to slow disease progression. Primary care physicians can play an important role in the diagnosis of glaucoma by referring patients with positive family history or with suspicious optic nerve head findings for complete ophthalmologic examination. They can improve treatment outcomes by reinforcing the importance of medication adherence and persistence and by recognizing adverse reactions from glaucoma medications and surgeries.
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              Diabetic Retinopathy: Pathophysiology and Treatments

              Diabetic retinopathy (DR) is the most common complication of diabetes mellitus (DM). It has long been recognized as a microvascular disease. The diagnosis of DR relies on the detection of microvascular lesions. The treatment of DR remains challenging. The advent of anti-vascular endothelial growth factor (VEGF) therapy demonstrated remarkable clinical benefits in DR patients; however, the majority of patients failed to achieve clinically-significant visual improvement. Therefore, there is an urgent need for the development of new treatments. Laboratory and clinical evidence showed that in addition to microvascular changes, inflammation and retinal neurodegeneration may contribute to diabetic retinal damage in the early stages of DR. Further investigation of the underlying molecular mechanisms may provide targets for the development of new early interventions. Here, we present a review of the current understanding and new insights into pathophysiology in DR, as well as clinical treatments for DR patients. Recent laboratory findings and related clinical trials are also reviewed.
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                Author and article information

                Contributors
                szmeyes@126.com
                panghtoyezz@zzu.edu.cn
                Journal
                Cell Biosci
                Cell Biosci
                Cell & Bioscience
                BioMed Central (London )
                2045-3701
                9 May 2024
                9 May 2024
                2024
                : 14
                : 59
                Affiliations
                [1 ]GRID grid.414011.1, ISNI 0000 0004 1808 090X, Department of Ophthalmology, , Henan Eye Hospital, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, ; Zhengzhou, 450003 China
                [2 ]College of Medicine, Zhengzhou University, ( https://ror.org/04ypx8c21) Zhengzhou, 450001 China
                Article
                1236
                10.1186/s13578-024-01236-2
                11084033
                38725013
                6a046630-8e42-4c67-a8b8-a5771848a6f7
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 6 January 2024
                : 18 April 2024
                Funding
                Funded by: Health Science and Technology Innovation Outstanding Young Talents Training Program of Henan Province
                Award ID: YXKC2021027
                Award Recipient :
                Funded by: Basic Research Project of Henan Eye Institute
                Award ID: 20JCZD001
                Award ID: 21JCZD002
                Award Recipient :
                Funded by: Science and Technology Major Project of Henan Province
                Award ID: 221100310200
                Award Recipient :
                Funded by: Central Plains Science and Technology Leading Talent Fund
                Award ID: 224200510013
                Award Recipient :
                Categories
                Review
                Custom metadata
                © Society of Chinese Bioscientists in America (SCBA) 2024

                Cell biology
                therapeutics,camkii,neurodegeneration,photoreceptor,diabetic retinopathy
                Cell biology
                therapeutics, camkii, neurodegeneration, photoreceptor, diabetic retinopathy

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