ABSTRACT
Diabetic retinopathy (DR) is the most common diabetic neurovascular complication, and the leading cause of preventable blindness among working-age individuals. Recently, agmatine, the endogenous decarboxylated L-arginine, has gained attention as a pleiotropic agent that modulates the diabetes-associated decline in quality of life, and exhibited varied protective biological effects. Diabetes was induced by a single streptozotocin (STZ, 50 mg/kg, i.p.) injection. When diabetes was verified, the animals were randomly allocated into three groups (16 rat each); diabetic, agmatine-treated diabetic (1 mg/kg, daily, for 12 weeks), and control group. Blood glucose homeostasis, retinal redox status, apoptotic parameters, nitric oxide synthase (NOS), nitric oxide (NO), vascular endothelial growth factor (VEGF), glutamate, glutamine, glutamine synthase (GS) activity, nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and mitogen-activated protein kinase (MAPKs) pathways were assayed biochemically. Retinal vascular permeability was measured. Retinal morphology was evaluated by hematoxylin and eosin staining. Retinal N-methyl-D-aspartic acid receptor1 (NMDAR1) and glutamate aspartate transporter (GLAST) mRNA were quantified. Glucose transporter 1, pro-caspase3, and glial fibrillary acidic protein (GFAP) expression were quantified by immunohistochemistry. Chronic agmatine treatment abrogated STZ-induced retinal neurodegeneration features including gliosis, and neuronal apoptosis, restored retinal vascular permeability, mostly through antioxidant, anti-apoptotic capacity, abolishing glutamate excitotoxicity, modulating the activity of NMDARs, MAPKs/NFκB, and NOS/NO pathways. By restoring the molecular and functional background of retinal neurovascular homeostatic balance, agmatine would be appropriate therapeutic option acting upstream of the DR, impeding its progression.
Subject(s)
Agmatine/pharmacology , Antioxidants/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Diabetic Retinopathy/drug therapy , Hypoglycemic Agents/pharmacology , Neuroprotective Agents/pharmacology , Retina/drug effects , Animals , Blood Glucose/metabolism , Caspase 3/genetics , Caspase 3/metabolism , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/genetics , Diabetes Mellitus, Experimental/pathology , Diabetic Retinopathy/chemically induced , Diabetic Retinopathy/genetics , Diabetic Retinopathy/pathology , Excitatory Amino Acid Transporter 1/genetics , Excitatory Amino Acid Transporter 1/metabolism , Gene Expression Regulation/drug effects , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Glucose Transporter Type 1/genetics , Glucose Transporter Type 1/metabolism , Glutamate-Ammonia Ligase/genetics , Glutamate-Ammonia Ligase/metabolism , Glutamic Acid/metabolism , Male , NF-kappa B/genetics , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type I/genetics , Nitric Oxide Synthase Type I/metabolism , Oxidative Stress , Rats , Receptors, N-Methyl-D-Aspartate/genetics , Receptors, N-Methyl-D-Aspartate/metabolism , Retina/metabolism , Retina/pathology , Streptozocin/administration & dosage , Treatment Outcome , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
OBJECTIVES: To assess periarticular bone changes in psoriasis patients with or without joint involvement and its effect on patients' quality of life (QoL). METHODS: This cross-sectional study enrolled 50 patients with psoriasis (25 only with skin psoriasis (PsO) and 25 with psoriatic arthritis (PsA)), as well as 25 healthy controls. All participants were analyzed by high-resolution computed tomography (HR-CT) scans of the dominant hand (second and third metacarpophalangeal joints) for detection of new bone formation (enthesophytes) and erosions. Demographic, laboratory, clinical, and disease-specific data, including physical function and QoL, were collected. RESULTS: Physical function and QoL scores were significantly worse in the PsA patients than in the PsO patients. All 25 PsA patients (100%), 18 PsO patients (72%), and 5 healthy individuals (20%) had periarticular bone changes. Statistically significant higher erosion number and volume as well as higher enthesophyte number and height were found in PsA patients compared to both PsO patients and controls, and in PsO patients compared to controls. In PsO patients, the number of erosions and enthesophytes had a negative correlation with some Short Form (SF)-36 sub-scores. In the PsA patients, the number of erosions had a positive correlation with psoriasis disability index, while the number of enthesophytes had a negative correlation with the general health SF-36 sub-score. CONCLUSION: In PsO patients, there may be subclinical periarticular inflammation (erosions and enthesophytes) that raise the suspicion of occult PsA or the possibility of PsO transition to PsA and these periarticular bone changes may worsen QoL in PsO patients. Key Points ⢠Skin psoriasis patients may have subclinical PsA. ⢠Periarticular bone changes in PsO patients may be the early sign for uploading PsA disease. ⢠Quality of life is highly affected in PsA than in PsO patients.
