Submit to Special Issue Submit Abstract to Special Issue Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

Emerging Roles of Inflammation in Retinal and Optic Nerve Pathologies

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 October 2024 | Viewed by 4397

Share This Special Issue

Special Issue Editors

Prof. Dr. Valery Shestopalov

E-Mail Website
Guest Editor

Department of Ophthalmology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA
Interests: neuroinflammation, responses in neurodegenerative disorders of the retina and optic nerve; accelerated ageing and cellular senescence in mechanically stressed cells; purinergic signaling and channelopathies in retinal neurobiology and vision disorders; translational studies on biomarkers in neurological disorders; therapeutic modulation of disease-causative pathways, new therapeutic targets and disease biomarkers in glaucoma research; animal models of neurodegenerative disorders; bioinformatics and pathway analysis of OMICS data; human microbiome in ocular health and disease; lens development and cataract formation

Prof. Dr. Claire H. Mitchell

E-Mail Website
Guest Editor

Department of Basic & Translational Sciences, University of Pennsylvania, Philadelphia, PA, USA
Interests: neurodegeneration; lysosomes; purinergic signaling; aging cell; neuroinflammation; microglia; retina
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Rob Nickells

E-Mail Website
Guest Editor

Ophthalmology and Visual Sciences, University of Wisconsin - Madison, Madison, WI, USA
Interests: glaucoma; retinal cell death; ganglion cell loss

Special Issue Information

Dear Colleagues,

Eye diseases affecting the retina and optic nerve are cumulatively responsible for nearly 20% of the global burden of blindness, with three major ones being age-related macular degeneration, diabetic retinopathy and glaucoma. Degenerations of photoreceptors and retinal pigment epithelium (RPE) in age-related macular degeneration (AMD), diabetic retinopathy and retinitis pigmentosa cause blindness through the dysfunction of the outer retina causing loss of photoreceptors. Progressive optic nerve degeneration in glaucomatous, ischemic and traumatic optic neuropathies, as well as multiple sclerosis and optic nerve injuries result in visual field loss and irreversible blindness due to retrograde death of retinal ganglion cells. Diverse mechanisms, molecular mechanisms and cell interactions are implicated in each of these pathologies; however, major risk factors including genetics, impaired regulation of blood circulation, mitochondrial dysfunction, chronic neuroinflammation, stress, etc., are commonly present and significantly affecting the outcome. The majority of people with vision impairment and blindness are over the age of 50 years, strongly indicating the involvement of cellular senescence, oxidative stress and immune system dysregulation. An in-depth understanding and prioritization of the mechanisms commonly guides researchers towards innovative treatment paradigms of vision preservation through neuroprotection. This Special Issue focuses on the key pathological mechanisms, both disease-unique and common ones, underlying diverse optic nerve and retinal degenerations, as well as the emerging therapeutic strategies targeting them.

Prof. Dr. Valery Shestopalov
Prof. Dr. Claire H. Mitchell
Prof. Dr. Rob Nickells
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

retina
optic nerve
neurodegeneration
disease mechanisms
neuroprotection
inflammation
senescence

Published Papers (4 papers)

Download All Papers

Research

Jump to: Review

15 pages, 2691 KiB

Open AccessArticle

Contralateral Astrocyte Response to Acute Optic Nerve Damage Is Mitigated by PANX1 Channel Activity

by Jasmine A. Wurl, Caitlin E. Mac Nair, Joel A. Dietz, Valery I. Shestopalov and Robert W. Nickells

Int. J. Mol. Sci. 2023, 24(21), 15641; https://doi.org/10.3390/ijms242115641 - 27 Oct 2023

Viewed by 741

Abstract

Glial reactivity is considered a hallmark of damage-induced innate immune responses in the central nervous system. In the visual system, unilateral optic nerve damage elicits dramatic glial reactivity in the retina directly affected by the lesion and a similar, albeit more modest, effect in the contralateral eye. Evaluation of astrocyte changes in a mouse model of optic nerve crush indicates that astrocyte reactivity, as a function of retinal coverage and cellular hypertrophy, occurs within both the experimental and contralateral retinas, although the hypertrophic response of the astrocytes in the contralateral eyes is delayed for at least 24 h. Evaluation of astrocytic reactivity as a function of Gfap expression indicates a similar, muted but significant, response in contralateral eyes. This constrained glial response is completely negated by conditional knock out of Panx1 in both astrocytes and Müller cells. Further studies are required to identify if this is an autocrine or a paracrine suppression of astroglial reactivity. Full article

(This article belongs to the Special Issue Emerging Roles of Inflammation in Retinal and Optic Nerve Pathologies)

► Show Figures

Figure 1

15 pages, 5755 KiB

Open AccessArticle

Various Forms of Programmed Cell Death Are Concurrently Activated in the Population of Retinal Ganglion Cells after Ischemia and Reperfusion

by Galina Dvoriantchikova, Emily Adis, Karin Lypka and Dmitry Ivanov

Int. J. Mol. Sci. 2023, 24(12), 9892; https://doi.org/10.3390/ijms24129892 - 08 Jun 2023

Cited by 4 | Viewed by 1366

Abstract

Retinal ischemia–reperfusion (IR)—which ultimately results in retinal ganglion cell (RGC) death—is a common cause of visual impairment and blindness worldwide. IR results in various types of programmed cell death (PCD), which are of particular importance since they can be prevented by inhibiting the activity of their corresponding signaling cascades. To study the PCD pathways in ischemic RGCs, we used a mouse model of retinal IR and a variety of approaches including RNA-seq analysis, knockout animals, and animals treated with an iron chelator. In our RNA-seq analysis, we utilized RGCs isolated from retinas 24 h after IR. In ischemic RGCs, we found increased expression of many genes that regulate apoptosis, necroptosis, pyroptosis, oxytosis/ferroptosis, and parthanatos. Our data indicate that genetic ablation of death receptors protects RGCs from IR. We showed that the signaling cascades regulating ferrous iron (Fe²⁺) metabolism undergo significant changes in ischemic RGCs, leading to retinal damage after IR. This data suggests that the activation of death receptors and increased Fe²⁺ production in ischemic RGCs promote the simultaneous activation of apoptosis, necroptosis, pyroptosis, oxytosis/ferroptosis, and parthanatos pathways. Thus, a therapy is needed that concurrently regulates the activity of the multiple PCD pathways to reduce RGC death after IR. Full article

(This article belongs to the Special Issue Emerging Roles of Inflammation in Retinal and Optic Nerve Pathologies)

► Show Figures

Figure 1

Review

Jump to: Research

20 pages, 819 KiB

Open AccessReview

The Role of Complement Dysregulation in Glaucoma

by Cindy Hoppe and Meredith Gregory-Ksander

Int. J. Mol. Sci. 2024, 25(4), 2307; https://doi.org/10.3390/ijms25042307 - 15 Feb 2024

Cited by 1 | Viewed by 790

Abstract

Glaucoma is a progressive neurodegenerative disease characterized by damage to the optic nerve that results in irreversible vision loss. While the exact pathology of glaucoma is not well understood, emerging evidence suggests that dysregulation of the complement system, a key component of innate immunity, plays a crucial role. In glaucoma, dysregulation of the complement cascade and impaired regulation of complement factors contribute to chronic inflammation and neurodegeneration. Complement components such as C1Q, C3, and the membrane attack complex have been implicated in glaucomatous neuroinflammation and retinal ganglion cell death. This review will provide a summary of human and experimental studies that document the dysregulation of the complement system observed in glaucoma patients and animal models of glaucoma driving chronic inflammation and neurodegeneration. Understanding how complement-mediated damage contributes to glaucoma will provide opportunities for new therapies. Full article

(This article belongs to the Special Issue Emerging Roles of Inflammation in Retinal and Optic Nerve Pathologies)

► Show Figures

Figure 1

15 pages, 1206 KiB

Open AccessReview

The Fibro-Inflammatory Response in the Glaucomatous Optic Nerve Head

by Emma K. Geiduschek and Colleen M. McDowell

Int. J. Mol. Sci. 2023, 24(17), 13240; https://doi.org/10.3390/ijms241713240 - 26 Aug 2023

Viewed by 944

Abstract

Glaucoma is a progressive disease and the leading cause of irreversible blindness. The limited therapeutics available are only able to manage the common risk factor of glaucoma, elevated intraocular pressure (IOP), indicating a great need for understanding the cellular mechanisms behind optic nerve head (ONH) damage during disease progression. Here we review the known inflammatory and fibrotic changes occurring in the ONH. In addition, we describe a novel mechanism of toll-like receptor 4 (TLR4) and transforming growth factor beta-2 (TGFβ2) signaling crosstalk in the cells of the ONH that contribute to glaucomatous damage. Understanding molecular signaling within and between the cells of the ONH can help identify new drug targets and therapeutics. Full article

(This article belongs to the Special Issue Emerging Roles of Inflammation in Retinal and Optic Nerve Pathologies)

► Show Figures