Background: Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis in the mammalian eye, thus suggesting that PEDF may protect against proliferative diabetic retinopathy. However, a role for PEDF in early diabetic retinopathy remains to be elucidated. We investigated here whether and how PEDF could prevent the development of diabetic retinopathy.
Methods: Streptozotocin-induced diabetic rats were treated with or without intravenous injection of PEDF for 4 weeks. Early neuronal derangements were evaluated by electroretinogram (ERG) and immunofluorescent staining of glial fibrillary acidic protein (GFAP). Expression of PEDF and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress, was localized by immunofluorescence. Vascular endothelial growth factor (VEGF) and p22phox expression were evaluated with western blots. Breakdown of blood retinal barrier (BRB) was quantified with fluorescein isothiocynate (FITC)-conjugated dextran. NADPH oxidase activity was measured with lucigenin luminescence.
Results: Retinal PEDF levels were reduced, and amplitudes of a- and b-wave in the ERG were decreased in diabetic rats, which were in parallel with GFAP overexpression in the Müller cells. Further, retinal 8-OHdG, p22phox and VEGF levels and NADPH oxidase activity were increased, and BRB was broken in diabetic rats. Administration of PEDF ameliorated all of the characteristic changes in early diabetic retinopathy.
Conclusions: Results suggest that PEDF could prevent neuronal derangements and vascular hyperpermeability in early diabetic retinopathy via inhibition of NADPH oxidase-driven oxidative stress generation. Substitution of PEDF may offer a promising strategy for halting the development of diabetic retinopathy.
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http://dx.doi.org/10.1002/dmrr.1007 | DOI Listing |
Invest Ophthalmol Vis Sci
January 2025
University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Coimbra, Portugal.
Purpose: Diabetic retinopathy (DR) is usually diagnosed many years after diabetes onset. Indeed, an early diagnosis of DR remains a notable challenge, and, thus, developing novel approaches for earlier disease detection is of utmost importance. We aim to explore the potential of texture analysis of optical coherence tomography (OCT) retinal images in detecting retinal changes in streptozotocin (STZ)-induced diabetic animals at "silent" disease stages when early retinal molecular and cellular changes that cannot be clinically detectable are already occurring.
View Article and Find Full Text PDFJ Vis Exp
December 2024
Department of Ophthalmology, Boston University Chobanian & Avedisian School of Medicine;
Ischemia-reperfusion injuries are known to cause a range of retinal pathologies, including diabetic retinopathy, glaucoma, retinal vascular occlusions, and other vaso-occlusive conditions. This manuscript presents a method for inducing ischemia-reperfusion injury in a mouse model. The method utilized anterior chamber cannulation attached to a saline reservoir, generating hydrostatic pressure to raise the intraocular pressure to 90-100 mmHg.
View Article and Find Full Text PDFFASEB J
January 2025
Department of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Retinal pathological angiogenesis (PA) is a common hallmark in proliferative retinopathies, including age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR), and retinopathy of prematurity (ROP). The mechanisms underlying PA is complex and incompletely understood. In this study, we investigated the role of extracellular matrix (ECM) protein biglycan (BGN) in PA using an oxygen-induced retinopathy (OIR) mouse model, along with hypoxia (1% O) conditions for incubating pericytes and endothelial cells in vitro.
View Article and Find Full Text PDFFront Clin Diabetes Healthc
December 2024
Department of Basic Sciences, College of Medicine, Sulaiman Al Rajhi University, Al-Bukairyah, Saudi Arabia.
Background: Complications of diabetes and its associated comorbidities can cause rapid progression of type II diabetes mellitus (T2DM). It comes at high costs and affects a patient's quality of life. We aim to assess T2DM in KSA, including the demographics, medications, complications, and comorbidities, as it remains an integral part of Vision 2030.
View Article and Find Full Text PDFCureus
December 2024
Internal Medicine, Kempegowda Institute of Medical Sciences, Bengaluru, IND.
Background Type 2 diabetes mellitus (T2DM) is associated with a high risk of developing microvascular complications such as diabetic nephropathy, diabetic neuropathy (DN), and diabetic retinopathy (DR), leading to significant morbidity. Early detection of these complications is crucial for improving patient outcomes. Neutrophil-lymphocyte ratio (NLR) and urine albumin-creatinine ratio (UACR) show promise as cost-effective and accessible biomarkers for the early detection of microvascular complications in T2DM.
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