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Ischemic Retinal Diseases: Pathophysiology, Retinal Imaging and Therapeutics
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Ischemic Retinal Diseases: Pathophysiology, Retinal Imaging and Therapeutics

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: closed (10 June 2024) | Viewed by 5745

Special Issue Editors

Prof. Dr. Kyriaki Thermos

E-Mail Website
Guest Editor
Department of Pharmacology, School of Medicine, University of Crete, 71003 Heraklion, Crete, Greece
Interests: diabetic retinopathy; AMPA excitotoxicity; neurodegeneration; neuroinflammation; vasculopathy; neuroprotection; endocannabinoid system; NADPH oxidases
Prof. Dr. Giovanni Casini

E-Mail Website
Guest Editor
Department of Biology, University of Pisa, Pisa, Italy
Interests: neuroprotection; physiology and pathology of the retina; physiology and pathology of the neurovascular unit; regulation of growth factor expression; nutraceuticals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Retinal ischemia leads to excitotoxicity and oxidative stress. The production of excessive reactive oxygen/nitrogen species (ROS/RNS) contributes to the induction of neurodegeneration, neuroinflammation, vasculopathy, and severe neovascularization, thus playing a major role in the pathogenesis of retinal diseases, such as age-related macular degeneration, diabetic retinopathy, glaucoma, and retinopathy of prematurity. Current therapies treat only the advanced stages of chronic retinal diseases. Many investigations focus on the development of new therapeutics, antioxidants, neuroprotectants, anti-inflammatory and vasculoprotective agents. Further technological advances in retinal imaging for screening the early pathology of retinal diseases and its progression, as well as the discovery of new therapeutics, are essential in improving the eyesight and quality of life of patients, as well as hampering the growing public health burden of retinal diseases. The main aim of this special issue is to attract contributions of “state-of-the-art” therapeutic interventions for the early stage of diseases and thus delay their progress to the advanced pathological stage where the eyesight of patients is compromised. At another level, the aim is to welcome contributions of new advances in retinal imaging that could make an impact in screening, identifying early disease pathologies, and selecting the appropriate neuroprotective drugs for implementing personalized treatments.

Prof. Dr. Kyriaki Thermos
Dr. Giovanni Casini
Guest Editors

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Keywords

  • retinal ischemia diseases
  • excitotoxicity
  • oxidative stress
  • neurodegeneration
  • neuroinflammation
  • vasculopathy
  • neuroprotection
  • antioxidants
  • age-related macular degeneration
  • diabetic retinopathy
  • glaucoma
  • retinopathy of prematurity
  • retinal imaging

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Published Papers (3 papers)

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Research

21 pages, 4959 KiB  
Article
Investigating the Effects of Exogenous and Endogenous 2-Arachidonoylglycerol on Retinal CB1 Cannabinoid Receptors and Reactive Microglia in Naive and Diseased Retina
by Sofia Papadogkonaki, Dimitris Spyridakos, Emmanouela Lapokonstantaki, Nikos Chaniotakis, Alexandros Makriyannis, Michael S. Malamas and Kyriaki Thermos
Int. J. Mol. Sci. 2023, 24(21), 15689; https://doi.org/10.3390/ijms242115689 - 28 Oct 2023
Cited by 1 | Viewed by 1476
Abstract
The endocannabinoid system (ECS) is a new target for the development of retinal disease therapeutics, whose pathophysiology involves neurodegeneration and neuroinflammation. The endocannabinoid 2-arachidonoylglycerol (2-AG) affects neurons and microglia by activating CB1/CB2 cannabinoid receptors (Rs). The aim of this study was to investigate [...] Read more.
The endocannabinoid system (ECS) is a new target for the development of retinal disease therapeutics, whose pathophysiology involves neurodegeneration and neuroinflammation. The endocannabinoid 2-arachidonoylglycerol (2-AG) affects neurons and microglia by activating CB1/CB2 cannabinoid receptors (Rs). The aim of this study was to investigate the effects of 2-AG on the CB1R expression/downregulation and retinal neurons/reactive microglia, when administered repeatedly (4 d), in three different paradigms. These involved the 2-AG exogenous administration (a) intraperitoneally (i.p.) and (b) topically and (c) by enhancing the 2-AG endogenous levels via the inhibition (AM11920, i.p.) of its metabolic enzymes (MAGL/ABHD6). Sprague Dawley rats were treated as mentioned above in the presence or absence of CB1/CB2R antagonists and the excitatory amino acid, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Immunohistochemistry, Western blot and a 2-AG level analyses were performed. The 2-AG repeated treatment (i.p.) induced the CB1R downregulation, abolishing its neuroprotective actions. However, 2-AG attenuated the AMPA-induced activation of microglia via the CB2R, as concurred by the AM630 antagonist effect. Topically administered 2-AG was efficacious as a neuroprotectant/antiapoptotic and anti-inflammatory agent. AM11920 increased the 2-AG levels providing neuroprotection against excitotoxicity and reduced microglial activation without affecting the CB1R expression. Our findings show that 2-AG, in the three paradigms studied, displays differential pharmacological profiles in terms of the downregulation of the CB1R and neuroprotection. All treatments, however, attenuated the activation of microglia via the CB2R activation, supporting the anti-inflammatory role of 2-AG in the retina. Full article
(This article belongs to the Special Issue Ischemic Retinal Diseases: Pathophysiology, Retinal Imaging and Therapeutics)
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13 pages, 2494 KiB  
Article
Mural Serum Response Factor (SRF) Deficiency Provides Insights into Retinal Vascular Functionality and Development
by Alexander Günter, Vithiyanjali Sothilingam, Michael M. Orlich, Alfred Nordheim, Mathias W. Seeliger and Regine Mühlfriedel
Int. J. Mol. Sci. 2023, 24(16), 12597; https://doi.org/10.3390/ijms241612597 - 9 Aug 2023
Cited by 1 | Viewed by 1634
Abstract
Serum response factor (SRF) controls the expression of muscle contraction and motility genes in mural cells (MCs) of the vasculature. In the retina, MC-SRF is important for correct angiogenesis during development and the continuing maintenance of the vascular tone. The purpose of this [...] Read more.
Serum response factor (SRF) controls the expression of muscle contraction and motility genes in mural cells (MCs) of the vasculature. In the retina, MC-SRF is important for correct angiogenesis during development and the continuing maintenance of the vascular tone. The purpose of this study was to provide further insights into the effects of MC SRF deficiency on the vasculature and function of the mature retina in SrfiMCKO mice that carry a MC-specific deletion of Srf. Retinal morphology and vascular integrity were analyzed in vivo via scanning laser ophthalmoscopy (SLO), angiography, and optical coherence tomography (OCT). Retinal function was evaluated with full-field electroretinography (ERG). We found that retinal blood vessels of these mutants exhibited different degrees of morphological and functional alterations. With increasing severity, we found vascular bulging, the formation of arteriovenous (AV) anastomoses, and ultimately, a retinal detachment (RD). The associated irregular retinal blood pressure and flow distribution eventually induced hypoxia, indicated by a negative ERG waveform shape. Further, the high frequency of interocular differences in the phenotype of individual SrfiMCKO mice points to a secondary nature of these developments far downstream of the genetic defect and rather dependent on the local retinal context. Full article
(This article belongs to the Special Issue Ischemic Retinal Diseases: Pathophysiology, Retinal Imaging and Therapeutics)
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17 pages, 9636 KiB  
Article
Large-Scale Protein Analysis of Experimental Retinal Artery Occlusion
by Nanna Vestergaard, Lasse Jørgensen Cehofski, Alexander Nørgård Alsing, Anders Kruse, Jonas Ellegaard Nielsen, Anders Schlosser, Grith Lykke Sorensen, Bent Honoré and Henrik Vorum
Int. J. Mol. Sci. 2023, 24(9), 7919; https://doi.org/10.3390/ijms24097919 - 27 Apr 2023
Cited by 2 | Viewed by 1729
Abstract
Retinal artery occlusion (RAO) is a devastating condition with no effective treatment. The management of RAO could potentially be improved through an in-depth understanding of the molecular alterations in the condition. This study combined advanced proteomic techniques and an experimental model to uncover [...] Read more.
Retinal artery occlusion (RAO) is a devastating condition with no effective treatment. The management of RAO could potentially be improved through an in-depth understanding of the molecular alterations in the condition. This study combined advanced proteomic techniques and an experimental model to uncover the retinal large-scale protein profile of RAO. In 13 pigs, RAO was induced with an argon laser and confirmed by fluorescein angiography. Left eyes serving as controls received a sham laser without inducing occlusion. Retinal samples were collected after one, three, or six days and analyzed with liquid chromatography—tandem mass spectrometry. In RAO, 36 proteins were differentially regulated on day one, 86 on day three, and 557 on day six. Upregulated proteins included clusterin, vitronectin, and vimentin, with several proteins increasing over time with a maximum on day six, including clusterin, vimentin, osteopontin, annexin-A, signal transducer, and the activator of transcription 3. On day six, RAO resulted in the upregulation of proteins involved in cellular response to stress, hemostasis, innate immune response, and cytokine signaling. Downregulated proteins were involved in transmission across chemical synapses and visual phototransduction. This study identified the upregulation of multiple inflammatory proteins in RAO and the downregulation of proteins involved in visual pathways. Full article
(This article belongs to the Special Issue Ischemic Retinal Diseases: Pathophysiology, Retinal Imaging and Therapeutics)
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