Progress in Retinal and Eye Research最新文献

{"title":"The OCT angular sign of Henle fiber layer (HFL) hyperreflectivity (ASHH) and the pathoanatomy of the HFL in macular disease","authors":"Prithvi Ramtohul ,&nbsp;Diogo Cabral ,&nbsp;SriniVas Sadda ,&nbsp;K. Bailey Freund ,&nbsp;David Sarraf","doi":"10.1016/j.preteyeres.2022.101135","DOIUrl":"10.1016/j.preteyeres.2022.101135","url":null,"abstract":"<div><p><span><span>The Henle fiber layer (HFL) is comprised of bundles of unmyelinated photoreceptor<span> axons intermingled with outer Müller cell processes. The photoreceptor axons extend from the cell bodies<span><span> located in the outer nuclear layer and radially project toward the </span>outer plexiform layer, the inner third of which includes the synaptic junctional complexes and the outer two-thirds of which includes the HFL. The oblique path of the HFL provides unique structural and reflectance properties and this radial </span></span></span>anatomy<span> is highlighted in many macular disorders<span> including those with macular star exudation and HFL hemorrhage. Recent investigations using multimodal imaging techniques, especially cross sectional and </span></span></span><em>en face</em><span> optical coherence tomography<span> (OCT), have provided new perspectives regarding HFL disruption in retinal diseases. The aim of this review is to highlight the pathoanatomy and multimodal imaging, especially OCT, associated with HFL disruption that is present in various macular diseases. After describing the current knowledge of the embryology, anatomy, and physiology of the HFL, we review the existing imaging modalities that allow </span></span><em>in vivo</em> visualization of the HFL in the healthy and diseased retina. Finally, we report the clinical and imaging findings of acute HFL alteration in various macular disorders, including degenerative, inflammatory, and vascular conditions. Also, we propose a novel and signature OCT biomarker indicative of acute photoreceptor disruption involving the HFL, termed the “angular sign of HFL hyperreflectivity” (ASHH) of macular disease, to unify the pathoanatomy common to these various macular disorders and to provide clarity regarding the underlying pathogenesis.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"95 ","pages":"Article 101135"},"PeriodicalIF":17.8,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9776062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating glial responses to products of diabetes-associated systemic dyshomeostasis","authors":"Dolly Ann Padovani-Claudio ,&nbsp;Carla J. Ramos ,&nbsp;Megan E. Capozzi ,&nbsp;John S. Penn","doi":"10.1016/j.preteyeres.2022.101151","DOIUrl":"10.1016/j.preteyeres.2022.101151","url":null,"abstract":"<div><p>Diabetic retinopathy (<strong>DR</strong>) is a leading cause of blindness in working age adults. DR has non-proliferative stages, characterized in part by retinal neuroinflammation and ischemia, and proliferative stages, characterized by retinal angiogenesis. Several systemic factors, including poor glycemic control, hypertension, and hyperlipidemia, increase the risk of DR progression to vision-threatening stages. Identification of cellular or molecular targets in early DR events could allow more prompt interventions pre-empting DR progression to vision-threatening stages.</p><p>Glia mediate homeostasis and repair. They contribute to immune surveillance and defense, cytokine and growth factor production and secretion, ion and neurotransmitter balance, neuroprotection, and, potentially, regeneration. Therefore, it is likely that glia orchestrate events throughout the development and progression of retinopathy. Understanding glial responses to products of diabetes-associated systemic dyshomeostasis may reveal novel insights into the pathophysiology of DR and guide the development of novel therapies for this potentially blinding condition.</p><p>In this article, first, we review normal glial functions and their putative roles in the development of DR. We then describe glial transcriptome alterations in response to systemic circulating factors that are upregulated in patients with diabetes and diabetes-related comorbidities; namely glucose in hyperglycemia, angiotensin II in hypertension, and the free fatty acid palmitic acid in hyperlipidemia. Finally, we discuss potential benefits and challenges associated with studying glia as targets of DR therapeutic interventions.</p><p><em>In vitro</em> stimulation of glia with glucose, angiotensin II and palmitic acid suggests that: 1) astrocytes may be more responsive than other glia to these products of systemic dyshomeostasis; 2) the effects of hyperglycemia on glia are likely to be largely osmotic; 3) fatty acid accumulation may compound DR pathophysiology by promoting predominantly proinflammatory and proangiogenic transcriptional alterations of macro and microglia; and 4) cell-targeted therapies may offer safer and more effective avenues for DR treatment as they may circumvent the complication of pleiotropism in retinal cell responses.</p><p>Although several molecules previously implicated in DR pathophysiology are validated in this review, some less explored molecules emerge as potential therapeutic targets. Whereas much is known regarding glial cell activation, future studies characterizing the role of glia in DR and how their activation is regulated and sustained (independently or as part of retinal cell networks) may help elucidate mechanisms of DR pathogenesis and identify novel drug targets for this blinding disease.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"94 ","pages":"Article 101151"},"PeriodicalIF":17.8,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10274102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo application of base and prime editing to treat inherited retinal diseases","authors":"Dong Hyun Jo ,&nbsp;Sangsu Bae ,&nbsp;Hyongbum Henry Kim ,&nbsp;Jin-Soo Kim ,&nbsp;Jeong Hun Kim","doi":"10.1016/j.preteyeres.2022.101132","DOIUrl":"10.1016/j.preteyeres.2022.101132","url":null,"abstract":"<div><p><span><span><span>Inherited retinal diseases (IRDs) are vision-threatening retinal disorders caused by pathogenic variants of genes related to visual functions. Genomic analyses </span>in patients<span><span><span> with IRDs have revealed pathogenic variants which affect vision. However, treatment options for IRDs are limited to </span>nutritional supplements<span> regardless of genetic variants or gene-targeting approaches based on antisense oligonucleotides and adeno-associated virus vectors limited to targeting few genes. </span></span>Genome editing<span><span>, particularly that involving clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 technologies, can correct pathogenic variants and provide additional treatment opportunities. Recently developed base and prime editing platforms based on CRISPR-Cas9 technologies are promising for therapeutic genome editing because they do not employ double-stranded breaks (DSBs), which are associated with P53 activation, large deletions, and </span>chromosomal translocations. Instead, using attached </span></span></span>deaminases<span> and reverse transcriptases, base and prime editing efficiently induces specific base substitutions and intended genetic changes (substitutions, deletions, or insertions), respectively, without DSBs. In this review, we will discuss the recent </span></span><em>in vivo</em> application of CRISPR-Cas9 technologies, focusing on base and prime editing, in animal models of IRDs.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"94 ","pages":"Article 101132"},"PeriodicalIF":17.8,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9623772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential therapeutic targets for age-related macular degeneration: The nuclear option","authors":"Mayur Choudhary ,&nbsp;Goldis Malek","doi":"10.1016/j.preteyeres.2022.101130","DOIUrl":"10.1016/j.preteyeres.2022.101130","url":null,"abstract":"<div><p>The functions and activities of nuclear receptors, the largest family of transcription factors in the human genome, have classically focused on their ability to act as steroid and hormone sensors in endocrine organs. However, they are responsible for a diverse array of physiological functions, including cellular homeostasis and metabolism, during development and aging. Though the eye is not a traditional endocrine organ, recent studies have revealed high expression levels of nuclear receptors in cells throughout the posterior pole. These findings have precipitated an interest in investigating the role of these transcription factors in the eye as a function of age and ocular disease, in particular age-related macular degeneration (AMD). As the leading cause of vision impairment in the elderly, identifying signaling pathways that may be targeted for AMD therapy is of great importance, given the lack of therapeutic options for over 85% of patients with this disease. Herein we review this relatively new field and recent findings supporting the hypothesis that the eye is a secondary endocrine organ, in which nuclear receptors serve as the bedrock for biological processes in cells vulnerable in AMD, including retinal pigment epithelial and choroidal endothelial cells, and discuss the therapeutic potential of targeting these receptors for AMD.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"94 ","pages":"Article 101130"},"PeriodicalIF":17.8,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10082136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9978527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian clock organization in the retina: From clock components to rod and cone pathways and visual function","authors":"Jacob D. Bhoi ,&nbsp;Manvi Goel ,&nbsp;Christophe P. Ribelayga ,&nbsp;Stuart C. Mangel","doi":"10.1016/j.preteyeres.2022.101119","DOIUrl":"10.1016/j.preteyeres.2022.101119","url":null,"abstract":"<div><p><span><span>Circadian (24-h) clocks are cell-autonomous biological oscillators that orchestrate many aspects of our physiology on a daily basis. Numerous circadian rhythms in mammalian and non-mammalian retinas have been observed and the presence of an endogenous circadian clock has been demonstrated. However, how the clock and associated rhythms assemble into pathways that support and control retina function remains largely unknown. Our goal here is to review the current status of our knowledge and evaluate recent advances. We describe many previously-observed retinal rhythms, including circadian rhythms of morphology, biochemistry, physiology, and gene expression. We evaluate evidence concerning the location and molecular machinery of the retinal circadian clock, as well as consider findings that suggest the presence of multiple clocks. Our primary focus though is to describe in depth circadian rhythms in the light responses of retinal neurons<span> with an emphasis on clock control of rod and cone pathways. We examine evidence that specific biochemical mechanisms produce these daily light response changes. We also discuss evidence for the presence of multiple circadian retinal pathways involving rhythms in neurotransmitter activity, transmitter receptors, metabolism, and pH. We focus on distinct actions of two </span></span>dopamine receptor systems in the outer retina, a dopamine D</span>₄<span> receptor system that mediates circadian control of rod/cone gap junction coupling and a dopamine D</span>₁<span> receptor system that mediates non-circadian, light/dark adaptive regulation of gap junction coupling between horizontal cells. Finally, we evaluate the role of circadian rhythmicity in retinal degeneration and suggest future directions for the field of retinal circadian biology.</span></p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"94 ","pages":"Article 101119"},"PeriodicalIF":17.8,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10660451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Homeostatic plasticity in the retina","authors":"Michael J. Fitzpatrick ,&nbsp;Daniel Kerschensteiner","doi":"10.1016/j.preteyeres.2022.101131","DOIUrl":"10.1016/j.preteyeres.2022.101131","url":null,"abstract":"<div><p><span>Vision begins in the retina, whose intricate neural circuits extract salient features of the environment from the light entering our eyes. Neurodegenerative diseases of the retina (e.g., inherited </span>retinal degenerations<span>, age-related macular degeneration, and glaucoma) impair vision and cause blindness<span> in a growing number of people worldwide. Increasing evidence indicates that homeostatic plasticity (i.e., the drive of a neural system to stabilize its function) can, in principle, preserve retinal function in the face of major perturbations, including neurodegeneration. Here, we review the circumstances and events that trigger homeostatic plasticity in the retina during development, sensory experience, and disease. We discuss the diverse mechanisms that cooperate to compensate and the set points and outcomes that homeostatic retinal plasticity stabilizes. Finally, we summarize the opportunities and challenges for unlocking the therapeutic potential of homeostatic plasticity. Homeostatic plasticity is fundamental to understanding retinal development and function and could be an important tool in the fight to preserve and restore vision.</span></span></p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"94 ","pages":"Article 101131"},"PeriodicalIF":17.8,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9676824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Studies of the retinal microcirculation using human donor eyes and high-resolution clinical imaging: Insights gained to guide future research in diabetic retinopathy","authors":"Chandrakumar Balaratnasingam ,&nbsp;Dong An ,&nbsp;Martin Hein ,&nbsp;Paula Yu ,&nbsp;Dao-Yi Yu","doi":"10.1016/j.preteyeres.2022.101134","DOIUrl":"10.1016/j.preteyeres.2022.101134","url":null,"abstract":"<div><p><span><span><span>The microcirculation plays a key role in delivering oxygen to and removing </span>metabolic wastes<span><span><span> from energy-intensive retinal neurons. Microvascular changes are a hallmark feature of </span>diabetic retinopathy (DR), a major cause of irreversible </span>vision loss globally. Early investigators have performed landmark studies characterising the pathologic manifestations of DR. Previous works have collectively informed us of the clinical stages of DR and the retinal manifestations associated with devastating vision loss. Since these reports, major advancements in histologic techniques coupled with three-dimensional image processing has facilitated a deeper understanding of the structural characteristics in the healthy and diseased </span></span>retinal circulation<span><span>. Furthermore, breakthroughs in high-resolution retinal imaging have facilitated clinical translation of histologic knowledge to detect and monitor progression of microcirculatory disturbances with greater precision. </span>Isolated perfusion<span> techniques have been applied to human donor eyes to further our understanding of the cytoarchitectural characteristics of the normal human retinal circulation as well as provide novel insights into the pathophysiology of DR. Histology has been used to validate emerging </span></span></span><em>in vivo</em><span><span><span> retinal imaging techniques<span> such as optical coherence tomography angiography. This report provides an overview of our research on the human retinal microcirculation in the context of the current </span></span>ophthalmic literature. We commence by proposing a standardised histologic lexicon for characterising the human retinal microcirculation and subsequently discuss the pathophysiologic mechanisms underlying key manifestations of DR, with a focus on </span>microaneurysms<span> and retinal ischaemia. The advantages and limitations of current retinal imaging modalities as determined using histologic validation are also presented. We conclude with an overview of the implications of our research and provide a perspective on future directions in DR research.</span></span></p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"94 ","pages":"Article 101134"},"PeriodicalIF":17.8,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9980722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of retinal glial cells contributes to the degeneration of ganglion cells in experimental glaucoma","authors":"Yanying Miao ,&nbsp;Guo-Li Zhao ,&nbsp;Shuo Cheng,&nbsp;Zhongfeng Wang,&nbsp;Xiong-Li Yang","doi":"10.1016/j.preteyeres.2023.101169","DOIUrl":"10.1016/j.preteyeres.2023.101169","url":null,"abstract":"<div><p><span><span><span>Elevation of intraocular pressure (IOP) is a major risk factor for </span>neurodegeneration<span> in glaucoma. Glial cells<span><span>, which play an important role in normal functioning of retinal neurons, are well involved into retinal ganglion cell (RGC) degeneration in </span>experimental glaucoma<span> animal models generated by elevated IOP. In response to elevated IOP, mGluR I is first activated and Kir4.1 channels are subsequently inhibited, which leads to the activation of Müller cells. Müller cell activation is followed by a complex process, including proliferation, release of inflammatory and growth factors (gliosis). Gliosis is further regulated by several factors. Activated Müller cells contribute to </span></span></span></span>RGC degeneration through generating glutamate receptor-mediated </span>excitotoxicity<span><span><span>, releasing cytotoxic factors<span> and inducing microglia activation. Elevated IOP activates microglia, and following morphological and functional changes, these cells, as resident </span></span>immune cells<span><span> in the retina, show adaptive immune responses, including an enhanced release of pro-inflammatory factors (tumor neurosis<span> factor-α, interleukins<span><span>, etc.). These ATP and Toll-like receptor-mediated responses are further regulated by heat shock proteins<span><span>, CD200R, chemokine receptors, and metabotropic </span>purinergic receptors, may aggravate RGC loss. In the optic nerve head, </span></span>astrogliosis<span> is initiated and regulated by a complex reaction process, including purines, transmitters, </span></span></span></span>chemokines<span>, growth factors and cytokines, which contributes to RGC axon injury through releasing pro-inflammatory factors and changing </span></span></span>extracellular matrix in glaucoma. The effects of activated glial cells on RGCs are further modified by the interplay among different types of glial cells. This review is concluded by presenting an in-depth discussion of possible research directions in this field in the future.</span></p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"93 ","pages":"Article 101169"},"PeriodicalIF":17.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9139242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rhodopsin, light-sensor of vision","authors":"Klaus Peter Hofmann ,&nbsp;Trevor D. Lamb","doi":"10.1016/j.preteyeres.2022.101116","DOIUrl":"10.1016/j.preteyeres.2022.101116","url":null,"abstract":"<div><p>The light sensor of vertebrate scotopic (low-light) vision, rhodopsin, is a G-protein-coupled receptor comprising a polypeptide chain with bound chromophore, 11-<em>cis</em>-retinal, that exhibits remarkable physicochemical properties. This photopigment is extremely stable in the dark, yet its chromophore isomerises upon photon absorption with 70% efficiency, enabling the activation of its G-protein, transducin, with high efficiency. Rhodopsin's photochemical and biochemical activities occur over very different time-scales: the energy of retinaldehyde's excited state is stored in &lt;1 ps in retinal-protein interactions, but it takes milliseconds for the catalytically active state to form, and many tens of minutes for the resting state to be restored. In this review, we describe the properties of rhodopsin and its role in rod phototransduction. We first introduce rhodopsin's gross structural features, its evolution, and the basic mechanisms of its activation. We then discuss light absorption and spectral sensitivity, photoreceptor electrical responses that result from the activity of individual rhodopsin molecules, and recovery of rhodopsin and the visual system from intense bleaching exposures. We then provide a detailed examination of rhodopsin's molecular structure and function, first in its dark state, and then in the active Meta states that govern its interactions with transducin, rhodopsin kinase and arrestin. While it is clear that rhodopsin's molecular properties are exquisitely honed for phototransduction, from starlight to dawn/dusk intensity levels, our understanding of how its molecular interactions determine the properties of scotopic vision remains incomplete. We describe potential future directions of research, and outline several major problems that remain to be solved.</p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"93 ","pages":"Article 101116"},"PeriodicalIF":17.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9094526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amblyopia and the whole child","authors":"Eileen E. Birch ,&nbsp;Krista R. Kelly","doi":"10.1016/j.preteyeres.2023.101168","DOIUrl":"10.1016/j.preteyeres.2023.101168","url":null,"abstract":"<div><p><span>Amblyopia<span> is a disorder of neurodevelopment<span> that occurs when there is discordant binocular visual experience during the first years of life. While treatments are effective in improving </span></span></span>visual acuity<span>, there are significant individual differences in response to treatment that cannot be attributed solely to difference in adherence. In this considerable variability in response to treatment, we argue that treatment outcomes might be optimized by utilizing deep phenotyping of amblyopic deficits to guide alternative treatment choices. In addition, an understanding of the broader knock-on effects of amblyopia on developing visually-guided skills, self-perception, and quality of life will facilitate a whole person healthcare approach to amblyopia.</span></p></div>","PeriodicalId":21159,"journal":{"name":"Progress in Retinal and Eye Research","volume":"93 ","pages":"Article 101168"},"PeriodicalIF":17.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9998377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9086488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}