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Molecular Pathogenesis and Therapeutics in Retinopathy

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 January 2025 | Viewed by 1574

Special Issue Editor


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Guest Editor
Unit of Endocrinology, Isola Tiberina-Gemelli Isola Hospital, 00186 Rome, Italy
Interests: diabetic neuropathy; retinopathy; glucose monitoring

Special Issue Information

Dear Colleagues,

Diabetic retinopathy (DR) is the most common and severe microvascular complication of diabetes mellitus (DM) that may lead to vision damage to the retina and remains the leading cause of blindness in the most developed countries. Current treatments, including lasers, anti-vascular endothelial growth factor (VEGF) therapy, steroids, and vitrectomy, target the late stages of DR, when vision has already been significantly affected. Therefore, it is of fundamental importance to study the pathogenesis of the early stages of DR in order to identify novel and more efficient preventive and interventional strategies. In the last few years, the concept of DR as a microvascular disease has evolved, in that it is now considered a more complex diabetic complication, in which retinal neurodegeneration (RN) plays a significant role. A special emphasis was placed on the pathophysiology of the retinal neurovascular unit (NVU), examining the contributions of the microvascular and neural elements that changed the traditional view of this disease. The components of the NVU include different neural cell types (i.e., ganglion cells, amacrine cells, horizontal cells, and bipolar cells), glia (e.g., Müller cells and astrocytes), professional immune cells (e.g., microglia and perivascular macrophages), and vascular cells (e.g., endothelial cells and pericytes). The diabetic milieu is related to the impairment of the NVU, which is characterized by RN and early microvascular alterations. Therefore, RN currently represents an early component of DR, occurring earlier than clinically identifiable microvascular damage, and can be considered a real form of neuropathy.  

This Special Issue invites researchers to submit molecular and clinical research and review articles that address the progress and current knowledge on the pathogenesis of this disease, the impact of glucose metabolism on retinal neurodegeneration, and therapeutic approaches. Moreover, with this Special Issue, we hope to shed light on the possible relationship between neural–retina alterations and diabetic peripheral or central neuropathy. 

Dr. Fabiana Picconi
Guest Editor

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Keywords

  • retinal neurodegeneration
  • retinal neurovascular unit
  • diabetic retinopathy
  • diabetic neuropathy
  • diabetic milieu
  • glucose variability

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Published Papers (2 papers)

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Research

15 pages, 4780 KiB  
Article
Gliotic Response and Reprogramming Potential of Human Müller Cell Line MIO-M1 Exposed to High Glucose and Glucose Fluctuations
by Benedetta Russo, Giorgia D’Addato, Giulia Salvatore, Marika Menduni, Simona Frontoni, Luigi Carbone, Antonella Camaioni, Francesca Gioia Klinger, Massimo De Felici, Fabiana Picconi and Gina La Sala
Int. J. Mol. Sci. 2024, 25(23), 12877; https://doi.org/10.3390/ijms252312877 - 29 Nov 2024
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Abstract
Retinal neurodegeneration (RN), an early marker of diabetic retinopathy (DR), is closely associated with Müller glia cells (MGs) in diabetic subjects. MGs play a pivotal role in maintaining retinal homeostasis, integrity, and metabolic support and respond to diabetic stress. In lower vertebrates, MGs [...] Read more.
Retinal neurodegeneration (RN), an early marker of diabetic retinopathy (DR), is closely associated with Müller glia cells (MGs) in diabetic subjects. MGs play a pivotal role in maintaining retinal homeostasis, integrity, and metabolic support and respond to diabetic stress. In lower vertebrates, MGs have a strong regenerative response and can completely repair the retina after injuries. However, this ability diminishes as organisms become more complex. The aim of this study was to investigate the gliotic response and reprogramming potential of the human Müller cell line MIO-M1 cultured in normoglycemic (5 mM glucose, NG) and hyperglycemic (25 mM glucose, HG) conditions and then exposed to sustained high-glucose and glucose fluctuation (GF) treatments to mimic the human diabetic conditions. The results showed that NG MIO-M1 cells exhibited a dynamic activation to sustained high-glucose and GF treatments by increasing GFAP and Vimentin expression together, indicative of gliotic response. Increased expression of SHH and SOX2 were also observed, foreshadowing reprogramming potential. Conversely, HG MIO-M1 cells showed increased levels of the indexes reported above and adaptation/desensitization to sustained high-glucose and GF treatments. These findings indicate that MIO-M1 cells exhibit a differential response under various glucose treatments, which is dependent on the metabolic environment. The in vitro model used in this study, based on a well-established cell line, enables the exploration of how these responses occur in a controlled, reproducible system and the identification of strategies to promote neurogenesis over neurodegeneration. These findings contribute to the understanding of MGs responses under diabetic conditions, which may have implications for future therapeutic approaches to diabetes-associated retinal neurodegeneration. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Therapeutics in Retinopathy)
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15 pages, 2823 KiB  
Article
Proliferative Diabetic Retinopathy Microenvironment Drives Microglial Polarization and Promotes Angiogenesis and Fibrosis via Cyclooxygenase-2/Prostaglandin E2 Signaling
by Shuta Kishishita, Ayumi Usui-Ouchi, Yasuo Ouchi, Yuiko Hata, Nobuyuki Ebihara and Shintaro Nakao
Int. J. Mol. Sci. 2024, 25(20), 11307; https://doi.org/10.3390/ijms252011307 - 21 Oct 2024
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Abstract
Diabetic retinopathy (DR) is the leading cause of visual impairment, particularly in the proliferative form (proliferative DR [PDR]). The impact of the PDR microenvironment on microglia, which are the resident immune cells in the central nervous system, and the specific pathological changes it [...] Read more.
Diabetic retinopathy (DR) is the leading cause of visual impairment, particularly in the proliferative form (proliferative DR [PDR]). The impact of the PDR microenvironment on microglia, which are the resident immune cells in the central nervous system, and the specific pathological changes it may induce remain unclear. This study aimed to investigate the role of microglia in the progression of PDR under hypoxic and inflammatory conditions. We performed a comprehensive gene expression analysis using human-induced pluripotent stem cell-derived microglia under different stimuli (dimethyloxalylglycine (DMOG), lipopolysaccharide (LPS), and DMOG + LPS) to mimic the hypoxic inflammatory environment characteristic of PDR. Principal component analysis revealed distinct gene expression profiles, with 76 genes synergistically upregulated under combined stimulation. Notably, prostaglandin-endoperoxide synthase 2 (encoding cyclooxygenase (COX)-2) exhibited the most pronounced increase, leading to elevated prostaglandin E2 (PGE2) levels and driving pathological angiogenesis and inflammation via the COX-2/PGE2/PGE receptor 2 signaling axis. Additionally, the upregulation of the fibrogenic genes snail family transcriptional repressor 1 and collagen type I alpha 1 chain suggested a role for microglia in fibrosis. These findings underscore the critical involvement of microglia in PDR and suggest that targeting both the angiogenic and fibrotic pathways may present new therapeutic strategies for managing this condition. Full article
(This article belongs to the Special Issue Molecular Pathogenesis and Therapeutics in Retinopathy)
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