Emergent therapeutics for the treatment of diabetic macular edema DOI

Priya Shukla,

Matthew W. Russell,

Nikhil Das

et al.

Expert Review of Ophthalmology, Journal Year: 2024, Volume and Issue: 19(4), P. 261 - 270

Published: May 2, 2024

Introduction Diabetic macular edema (DME) is a vision threatening accumulation of fluid within the macula. Current treatments involve use intravitreal anti-vascular endothelial growth factor (anti-VEGF), steroids, and laser to preserve vision.

Language: Английский

Müller Glial Cells in the Macula: Their Activation and Cell-Cell Interactions in Age-Related Macular Degeneration DOI Creative Commons

Soumya Navneet,

Kyrie Wilson,

Bärbel Rohrer

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2024, Volume and Issue: 65(2), P. 42 - 42

Published: Feb. 28, 2024

Müller glia, the main glial cell of retina, are critical for neuronal and vascular homeostasis in retina. During age-related macular degeneration (AMD) pathogenesis, activation, remodeling, migrations reported areas retinal pigment epithelial (RPE) degeneration, photoreceptor loss, choroidal neovascularization (CNV) lesions. Despite this evidence indicating activation localized to regions AMD it is unclear whether these responses contribute pathology or occur merely as a bystander effect. In review, we summarize how glia affected retinas share prospect on stress might directly pathogenesis AMD. The goal review highlight need future studies investigating cell's role This may lead better understanding pathology, including conversion from dry wet AMD, which has no effective therapy currently shed light drug intolerance resistance current treatments.

Language: Английский

Citations

13

Current understanding of subclinical diabetic retinopathy informed by histology and high‐resolution in vivo imaging DOI Creative Commons
Martin Hein,

Hassanain Qambari,

Dong An

et al.

Clinical and Experimental Ophthalmology, Journal Year: 2024, Volume and Issue: 52(4), P. 464 - 484

Published: Feb. 16, 2024

The escalating incidence of diabetes mellitus has amplified the global impact diabetic retinopathy. There are known structural and functional changes in retina that precede fundus photography abnormalities which currently used to diagnose clinical Understanding these subclinical alterations is important for effective disease management. Histology high-resolution imaging reveal entire neurovascular unit, comprised retinal vasculature, neurons glial cells, affected disease. Early manifestations seen form blood flow electroretinography disturbances. Structurally, there cellular components glia neuronal network. On imaging, vessel density thickness layers observed. How disturbances interact ultimately manifest as remains elusive. However, this knowledge reveals potential early therapeutic targets need modalities can detect a setting.

Language: Английский

Citations

5

AQP4- and Kir4.1-Mediated Müller Cell Oedema Is Involved in Retinal Injury Induced By Hypobaric Hypoxia DOI
Cong Han, Yuting Li, Xingxing Zheng

et al.

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: unknown

Published: July 26, 2024

Language: Английский

Citations

5

Suppression of inner blood-retinal barrier breakdown and pathogenic Müller glia activation in ischemia retinopathy by myeloid cell depletion DOI Creative Commons
Lingli Zhou, Zhenhua Xu, Haining Lu

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Aug. 24, 2024

Abstract Ischemic retinopathies including diabetic retinopathy are major causes of vision loss. Inner blood-retinal barrier (BRB) breakdown with retinal vascular hyperpermeability results in macular edema. Although dysfunction the neurovascular unit neurons, glia, and cells is now understood to underlie this process, there a need for fuller elucidation underlying events BRB ischemic disease, systematic analysis myeloid exploration cellular cross-talk. We used an approach microglia depletion CSF-1R inhibitor PLX5622 (PLX) ischemia-reperfusion (IR) model. Under non-IR conditions, PLX treatment successfully depleted retina. suppressed microglial activation response following IR as well infiltration monocyte-derived macrophages. This occurred association reduction expression chemokines CCL2 inflammatory adhesion molecule ICAM-1 . In addition, was marked suppression neuroinflammation IL-1b , IL-6 Ptgs2 TNF-a Angpt2 protein that regulates permeability. significantly inner IR, without appreciable effect on neuronal dysfunction. A translatomic Müller glial-specific gene vivo using Ribotag demonstrated strong cell multiple pro-inflammatory genes treatment. Co-culture studies activated directly upregulates cell-expression these genes, indicating downstream effector IR. two types endothelial ability both compromise EC function. Interestingly, quiescent enhanced function co-culture system. Together demonstrates pivotal role setting ischemia-associated disease indicates play iBRB dysregulation, through direct indirect effects, while glia participate amplifying neuroinflammatory cells.

Language: Английский

Citations

5

Diabetic macular edema (DME): dissecting pathogenesis, prognostication, diagnostic modalities along with current and futuristic therapeutic insights DOI Creative Commons
Ahmed Sermed Al Sakini, Abdulrahman Khaldoon Hamid,

Zainab A. Alkhuzaie

et al.

International Journal of Retina and Vitreous, Journal Year: 2024, Volume and Issue: 10(1)

Published: Oct. 28, 2024

Abstract One of the most common health concerns disturbing people within working years globally is diabetes mellitus (DM). well-known consequence DM vascular damage, which can manifest as macro- and microangiopathy affecting ocular retina. Therefore, Diabetic macular edema (DME) a major sight-threatening complication diabetic retinopathy (DR) worldwide. It prevalent cause significant vision impairment in patients. Long-term loss be avoided by following early DME treatment guidelines everyday life. Hence, there are various therapeutic approaches for management. Currently, first-line anti-VEGF family drugs, such ranibizumab, brolucizumab, bevacizumab, aflibercept. Nevertheless, relapses disease, inadequate response, resistance during therapy still seen because intricate pathophysiological foundation disease. Consequently, an excellent requirement to advance become better at controlling diseases more satisfactorily require fewer treatments overall. We conducted thorough literature search current review present comprehensive overview primary data about agents. also covered novel advances management probable future being investigated developed. This recommended that Large clinical trials should afford sufficient evidence support these innovative modalities.

Language: Английский

Citations

5

Exploring the role of Müller cells-derived exosomes in diabetic retinopathy DOI
Mohamed S. Gad, Nehal M. Elsherbiny, Dalia R. El-Bassouny

et al.

Microvascular Research, Journal Year: 2024, Volume and Issue: 154, P. 104695 - 104695

Published: May 8, 2024

Language: Английский

Citations

4

Thymoquinone Mediates Müller Cell Apoptosis via miR-29b/SP1 Pathway: A Potential Therapeutic Approach in Diabetic Retinopathy DOI
Khalid M. Alkharfy, Ajaz Ahmad, Mohammad Raish

et al.

Drug Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract This study aims to explore the therapeutic potential of thymoquinone (TQ) in DR by assessing its effects on Müller cell apoptosis through modulation miR-29b/SP1 pathway a diabetic animal model. Healthy C57BL/6 mice (25 g) were used study. Retinal samples collected from both normal and subjected various treatments: TQ (1 mg/kg/day), glibenclamide (GLB, 250 sitagliptin (STG, 10 metformin (MET, 5 mg/kg/day) over period 28 days. The measured miR-29b SP1 mRNA levels using qRT-PCR. Protein expressions SP1, Bax, bcl-2 analyzed western blotting, while Caspase-3 activity an ELISA assay kit, annexin V. administration resulted 52% reduction blood glucose levels. Similarly, GLB, STG, MET treatments reduced 60%, 57%, 61%, respectively (p<0.05). In addition, upregulated 51.28% downregulated 32.52% Bax protein expression decreased 64.99%, Bcl-2 increased 62.92% treatment group as compared untreated controls. Furthermore, was 40.03% with Interestingly, effect inhibited blocker (p<0.05), mimic enhanced this effect; associated mitigation retinal cells flow cytometry These results indicate that might be possible option for via pathway; therefore, playing significant role mechanism against death.

Language: Английский

Citations

0

Kidins220-deficient hydrocephalus mice exhibit altered glial phenotypes and AQP4 differential regulation in the retina and optic nerve, with preserved retinal ganglion cell survival DOI Creative Commons
José A. Fernández‐Albarral, Ana Simón‐García, Elena Salobrar‐García

et al.

Fluids and Barriers of the CNS, Journal Year: 2025, Volume and Issue: 22(1)

Published: Feb. 12, 2025

Hydrocephalus, characterized by ventriculomegaly due to cerebrospinal fluid accumulation in the cerebral ventricles, is a co-morbidity factor several neurodevelopmental, psychiatric and neurodegenerative diseases. Aquaporin-4 (AQP4) crucial for brain water homeostasis, with Aqp4 knockout mice showing sporadic increased content. Kinase D interacting substrate of 220 kDa (Kidins220), transmembrane protein involved neuronal survival, synaptic activity neurogenesis, controls AQP4 levels ependymocytes astrocytes. Indeed, Kidins220 deficiency leads hydrocephalus downregulating VPS35, key component retromer complex, targeting lysosomal degradation. Importantly, ependymal barrier idiopathic normal pressure patients shows similar downregulation KIDINS220 AQP4. In addition, pathogenic variants gene are linked SINO syndrome, rare disorder spastic paraplegia, intellectual disability, nystagmus, obesity associated ventriculomegaly. Given retina's structural functional similarities brain, we hypothesized that would affect retinal regulation. However, diminished expression VPS35 retina Kidins220-deficient mice, did not cause edema or downregulate Müller cells. Surprisingly, there was an increase within this glial cell population. Conversely, optic nerve astrocytes reduced, as observed astrocytes, suggesting distinctive adaptive response glia retina. Furthermore, phenotypic modifications mice. find any signs damage Future studies using OCT OCTA syndrome will be essential elucidating relationship between variants, alterations, papilledema, visual function.

Language: Английский

Citations

0

Obesity‐related early structural alterations in the retina detected by optical coherence tomography DOI Creative Commons

Maide Gözde İnam,

Onur İnam,

Doru Gucer

et al.

Diabetes Obesity and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

This retrospective cross-sectional study, using retinal spectral-domain optical coherence tomography (SD-OCT) scans, investigated obesity-related structural alterations in the retina. Ninety-two eyes of 92 healthy asymptomatic participants were categorized into two groups based on body mass index (BMI) measurements: non-obese (BMI < 25, 45%) and pre-obese/obese ≥ 55%) to compare imaging parameters different layers. Structural parameters, including thickness volume values, obtained across distinct layers segmented SD-OCT scans. The nerve fibre layer was lower high-BMI group than low-BMI (p = 0.048). However, presented significantly higher inner nuclear 0.036). In region analysis, difference prominent superior 0.033) inferior 0.001) parafoveal nasal perifoveal 0.041) regions, while changes 0.009) regions. A stepwise hierarchical binary logistic regression model, controlling for age gender, pointed significant associations regionally decreased increased with high BMI 0.001). Retinal detected between healthy, individuals groups. Besides a layer, increase BMI, possibly due Müller glia responses osmotic, metabolic inflammatory stress, awaiting further investigation.

Language: Английский

Citations

0

The Role of Non-coding RNAs in Diabetic Retinopathy: Mechanistic Insights and Therapeutic Potential DOI

Zhuan Zuo,

Ni Li, Qian Zhang

et al.

Molecular Neurobiology, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0