Molecular Research on Diabetic Retinopathy (DR)

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 2017

Special Issue Editor


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Guest Editor
Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA
Interests: neuroscience; retinopathy

Special Issue Information

Dear Colleagues,

Diabetic retinopathy (DR) remains one of the leading causes of vision impairment worldwide and represents a complex neurovascular complication of diabetes. Increasing evidence indicates that DR is not only a microvascular disease but also involves early retinal neurodegeneration, chronic inflammation, oxidative stress, metabolic dysregulation, and altered neurovascular coupling. At the molecular level, dysregulated signaling pathways related to angiogenesis, immune activation, cell death, mitochondrial dysfunction, and epigenetic regulation play critical roles in disease initiation and progression.

In recent years, interdisciplinary approaches have expanded DR research beyond traditional ophthalmology. Advances in anesthesiology and pain research have provided new insights into perioperative metabolic stress, neuroinflammation, and microcirculatory dysfunction, all of which may influence retinal vulnerability in diabetic patients. Moreover, emerging experimental platforms, including retinal organoids, stem cell–derived models, and organ-on-a-chip systems, offer powerful tools to recapitulate human retinal pathology and to investigate disease mechanisms and therapeutic responses in a translationally relevant manner.

This Special Issue aims to collect high-quality original research and reviews focusing on the molecular mechanisms underlying diabetic retinopathy. Topics of interest include, but are not limited to, inflammation and oxidative stress, neurovascular unit dysfunction, metabolic and mitochondrial pathways, pain-related and anesthetic modulation of retinal injury, organoid-based disease modeling, biomarker discovery, and novel therapeutic targets. By integrating basic, translational, and interdisciplinary research, this Special Issue seeks to advance mechanistic understanding and promote innovative strategies for the prevention and treatment of diabetic retinopathy.

Dr. Siyuan Song
Guest Editor

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Keywords

  • diabetic retinopathy
  • molecular mechanisms
  • oxidative stress
  • inflammation
  • neurovascular unit
  • anesthesia and perioperative stress
  • pain and neuroinflammation
  • retinal organoids
  • therapeutic targets

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Published Papers (2 papers)

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Research

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13 pages, 1031 KB  
Article
Insulin Resistance-Related Traits and Diabetic Maculopathy: Causal Insights from Mendelian Randomization
by Young Lee, Je Hyun Seo and Sung Pyo Park
Biomedicines 2026, 14(6), 1178; https://doi.org/10.3390/biomedicines14061178 - 22 May 2026
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Abstract
Background/Objectives: To investigate the causal relationships linking body mass index (BMI) and circulating insulin-like growth factor 1 (IGF-1) levels with diabetic maculopathy risk using two-sample Mendelian randomization (MR). Methods: A two-sample MR framework was applied, utilizing genetic instruments for BMI and IGF-1 [...] Read more.
Background/Objectives: To investigate the causal relationships linking body mass index (BMI) and circulating insulin-like growth factor 1 (IGF-1) levels with diabetic maculopathy risk using two-sample Mendelian randomization (MR). Methods: A two-sample MR framework was applied, utilizing genetic instruments for BMI and IGF-1 derived from the UK Biobank. Summary-level diabetic maculopathy data were obtained from the FinnGen consortium. Genome-wide significant single-nucleotide polymorphisms (SNPs, p < 5.0 × 10−8) independently associated with each exposure were employed as instrumental variables. Primary causal estimates were obtained using the inverse-variance weighted (IVW) method. Sensitivity analyses, including MR-Egger regression, weighted median methods, and the MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), were conducted to evaluate robustness and potential pleiotropy. Results: Genetically predicted BMI was positively associated with diabetic maculopathy risk in both the IVW analysis (odds ratio [OR] = 1.16 (95% confidence interval [CI]: 1.04–1.30), p = 0.008) and MR-PRESSO (OR = 1.16 (95% CI: 1.04–1.28), p = 0.006). MR-PRESSO exhibited a significant relationship between higher IGF-1 levels and increased diabetic maculopathy risk (OR = 1.09 (95% CI: 1.01–1.18), p = 0.025), whereas the IVW method indicated only a suggestive association (OR = 1.08 (95% CI: 0.99–1.18), p = 0.087). Conclusions: The genetic evidence supports a causal role of insulin resistance-related traits in diabetic maculopathy development, with higher BMI and IGF-1 levels increasing diabetic maculopathy risk. These results underscore the potential contributory role of IGF-1 in disease pathogenesis and suggest that insulin resistance-related traits may represent preventive therapeutic targets. Full article
(This article belongs to the Special Issue Molecular Research on Diabetic Retinopathy (DR))
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Review

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37 pages, 2412 KB  
Review
Sympathetic Stress and Sleep Loss in Diabetic Retinopathy: Links to Retinal Blood-Flow Control
by Mengquan Tan, Shengtao Liu, Muxuan Fang, Man Yuan, Danping Niu, Yang Wang, Huixian Zhou, Jiling Zeng, Yaling Dai and Siyuan Song
Biomedicines 2026, 14(3), 736; https://doi.org/10.3390/biomedicines14030736 - 23 Mar 2026
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Abstract
Diabetic retinopathy (DR) is more than a capillary disorder. Diabetes affects neurons, glial cells, vascular cells, and immune signals within the retinal neurovascular unit (NVU). Retinal neurovascular coupling (NVC) is a useful functional marker of NVU integrity because it reflects the rise in [...] Read more.
Diabetic retinopathy (DR) is more than a capillary disorder. Diabetes affects neurons, glial cells, vascular cells, and immune signals within the retinal neurovascular unit (NVU). Retinal neurovascular coupling (NVC) is a useful functional marker of NVU integrity because it reflects the rise in local blood flow that follows neural activity. Many human flicker-light studies report smaller vessel dilation or weaker flow responses in diabetes. This finding can appear even in patients without clear fundus lesions. When NVC is reduced, retinal tissue may receive less oxygen. Lower oxygen delivery can raise oxidative stress and promote inflammation. These changes can then worsen vascular injury. This review describes key NVC pathways and diabetes-related NVU changes in Müller glia, astrocytes, microglia, pericytes, and endothelial cells. The review highlights sympathetic activation as a common stress signal. Pain, anxiety, perioperative stress, and sleep loss can increase sympathetic activity and circulating catecholamines. In the diabetic retina, vascular reserve is often limited. Under these conditions, catecholamines can increase mural cell constriction, reduce nitric oxide (NO)-dependent relaxation, and increase endothelial activation and barrier strain. These effects can shift the baseline state of glial and immune cells and further weaken NVC. The review also summarizes translational tools that can test these links. These tools include heart rate variability, standardized NVC protocols with diameter and flow measures, and retinal organoid and organ-on-a-chip platforms with controlled adrenergic exposure. The review discusses perioperative care packages that reduce stress responses, protect sleep, and manage glucose as practical ways to support retinal microcirculation. More longitudinal human studies are still needed. Retina-specific perioperative endpoints are also needed to clarify causality and to guide intervention trials. Full article
(This article belongs to the Special Issue Molecular Research on Diabetic Retinopathy (DR))
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