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Diabetic Retinopathy: From Molecular Mechanisms to Therapeutic Approach

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 (31 March 2025) | Viewed by 1694

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College of Medicine, University of Ulsan, Ulsan, Republic of Korea
Interests: neuropathic pain; mammalian target of rapamycin (mTOR); recombinant adeno-associated virus (rAAV); dorsal root ganglion (DRG)

Special Issue Information

Dear Colleagues,

As you know, Diabetic retinopathy (DR) is the leading cause of blindness in adults, caused by complex pathophysiology involving both vascular and neural components. Traditional treatments, including anti-VEGF agents and laser therapy, primarily focus on advanced stages of DR, yet limitations in treatment outcomes have also been reported. Therefore, this Special Issue aims to offer insights into disease progression prior to overt vascular damage by featuring the latest molecular mechanisms on the pathogenesis of DR, particularly early neurovascular and cellular mechanisms that have recently gained attention for their significance. By enhancing our understanding of retinal neurodegeneration and neurovascular unit dysfunction, we aim to contribute to the development of novel biomarkers, preventive strategies, and personalized therapeutic approaches that can greatly aid in DR management on the level of molecular research. This special issue thus seeks to bridge the gaps in current therapeutic approaches through a deeper understanding of DR. We welcome various submission types, including original research articles, and comprehensive reviews.

Dr. Heuiran Lee
Guest Editor

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Keywords

  • retinal neurodegeneration
  • diabetic retinopathy
  • diabetic retinopathy (DR) Pathogenesis
  • neurovascular unit (NVU) dysfunction
  • biomarkers in diabetic retinopathy
  • novel treatments for diabetic retinopathy

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Published Papers (1 paper)

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Research

16 pages, 3104 KB  
Article
The Protective Effect of Topical PACAP38 in Retinal Morphology and Function of Type 2 Diabetic Retinopathy
by Lina Li, Evelin Patko, Edina Szabo, Dorottya Molitor, Balazs Meresz, Dora Reglodi, Andras Varga, Diana Denes, Lei Dai, Hongjie Wang, Alexandra Vaczy and Tamas Atlasz
Int. J. Mol. Sci. 2025, 26(8), 3753; https://doi.org/10.3390/ijms26083753 - 16 Apr 2025
Viewed by 905
Abstract
The continuously growing diabetes population is a significant concern with type 2 diabetic retinal disease (T2DRD), which is a leading cause of permanent blindness. However, the underlying pathophysiological mechanism of T2DRD has not yet been fully understood. Pituitary adenylate cyclase-activating polypeptide (PACAP) was [...] Read more.
The continuously growing diabetes population is a significant concern with type 2 diabetic retinal disease (T2DRD), which is a leading cause of permanent blindness. However, the underlying pathophysiological mechanism of T2DRD has not yet been fully understood. Pituitary adenylate cyclase-activating polypeptide (PACAP) was first isolated from the ovine hypothalamus based on its stimulating effect on the adenylate cyclase enzyme in anterior pituitary cells. PACAP38 (PACAP with 38 amino acids) activates anti-apoptotic pathways, inhibits pro-apoptotic signaling, and creates an anti-inflammatory environment in the retina. The aim of the present study was to test the possible retinoprotective effect of the topical administration of PACAP38 in a type 2 diabetic animal model induced by a high-fat diet and the intraperitoneally injected low-dose streptozotocin (STZ). Wistar rats were divided into four groups: the control, control + PACAP38, diabetes, and diabetes + PACAP38 groups randomly. Type 2 diabetes was induced with the combination of STZ (30 mg/kg) and a high-fat diet. All rats were treated topically two times a day for 16 weeks: the control + PACAP38 and diabetes + PACAP38 groups were applied with PACAP38 eye drops (1 µg/drop), while the control and diabetes groups were administered using vehicles (artificial tears). The diabetes model was validated by a fasting oral glucose tolerance test (OGTT) and C-peptide ELISA test. Animals were monitored during the whole experiment for the progression of the disease using electroretinography (ERG) and optical coherence tomography (OCT). Post-mortem immunohistochemistry and a vessel analysis were performed in the retina samples after 16 weeks. An OGTT, a C-peptide ELISA test, and the investigation of blood parameters proved the development of type 2 diabetes. Significant differences could be detected in visual function between the two diabetic groups at week 16 (in the a-wave, b-wave, and OP amplitudes), where the diabetes PACAP38-treated group was similar to the control ones. OCT measurements correlated with ERG data, where the total retinal thickness was preserved in the diabetes + PACAP38 group. PACAP38 also protected the microvascular structure in the retina. Topically administered PACAP38 has potent neuroprotective effects against type 2 diabetic retinal disease; therefore, it could be a promising therapeutic approach for the treatment of T2DRD. Full article
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