scholarly journals Dysregulation of the OGF–OGFr pathway correlates with elevated serum OGF and ocular surface complications in the diabetic rat

2020 ◽  
Vol 245 (15) ◽  
pp. 1414-1421 ◽  
Author(s):  
Ian S Zagon ◽  
Joseph W Sassani ◽  
Indira Purushothaman ◽  
Patricia J McLaughlin
Keyword(s):  
Type 1 Diabetes ◽  
Growth Factor ◽  
Dry Eye ◽  
Ocular Surface ◽  
Surface Defects ◽  
Serum Levels ◽  
Male Rats ◽  
Corneal Surface ◽  
Surface Sensitivity

Diabetes often presents with ocular surface complications including dry eye, keratopathy, and altered sensitivity, along with systemic disorders. A common theme associated with corneal surface defects is decreased cellular proliferation. The opioid growth factor (OGF)–OGF receptor (OGFr) regulatory axis maintains epithelial homeostasis and can be modulated by naltrexone, an opioid receptor antagonist, to block OGF–OGFr interaction and increase cellular replication. Complete blockade using naltrexone accelerates cell proliferation, increases the rate of re-epithelialization in corneal surface abrasions, reverses dry eye, and restores corneal surface sensitivity in animal models of type 1 and type 2 diabetes. Data on the efficacy of naltrexone in these models suggest that the OGF–OGFr axis is dysregulated in diabetes. In the present study, we investigated the OGF–OGFr axis by assessing serum and tissue levels of OGF and OGFr during the development of streptozotocin-induced hyperglycemia and postulated a mechanism of action. We correlated the dysregulation of the OGF–OGFr axis with the onset and magnitude of corneal surface complications (e.g. tear fluid production, corneal surface sensitivity) in type 1 diabetes (T1D). Serum levels of OGF increased in both uncontrolled T1D and insulin-controlled (T1D-INS) male rats within four weeks of streptozotocin injection. Serum OGFr levels were significantly reduced in diabetic rats on weeks 3 and 8 post streptozotocin. Tear production was significantly reduced, and corneal sensitivity measurements were abnormal in both T1D and T1D-INS animals within four weeks of streptozotocin. Corneal re-epithelialization was delayed in T1D rats, but not in T1D-INS animals; however, expression levels of the inhibitory growth factor OGF and its receptor, OGFr, were elevated in the corneal epithelium more than 2-fold in both diabetic groups. These data demonstrate for the first time that dysregulation of the OGF–OGFr axis in the diabetic cornea is associated with the onset and magnitude of ocular surface complications. Impact statement This research extends our knowledge about the presence and role of the OGF–OGFr regulatory axis in type 1 diabetes (T1D) and demonstrates specific targets within the pathway that are dysregulated. Serum levels of OGF, an inhibitory growth factor, are significantly elevated in male T1D rats, and OGFr serum values are increased in T1D. The onset of elevated OGF corresponds to the onset of ocular surface complications including dry eye, delayed corneal epithelial repair, and abnormal corneal surface sensitivity in T1D. Systemic insulin does not protect against elevated OGF levels or the onset of dry eye and sensitivity. These data are the first to associate some ocular surface defects in T1D with alterations in the OGF–OGFr pathway.

scholarly journals Blockade of OGFr delays the onset and reduces the severity of diabetic ocular surface complications

2020 ◽  
pp. 153537022097206
Author(s):  
Ian S Zagon ◽  
Joseph W Sassani ◽  
Indira Purushothaman ◽  
Patricia J McLaughlin
Keyword(s):  
Growth Factor ◽  
Dry Eye ◽  
Ocular Surface ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Corneal Surface ◽  
Surface Sensitivity ◽  
Naltrexone Treatment

The opioid growth factor (OGF)–OGF receptor (OGFr) pathway is present in the ocular surface and functions to maintain homeostasis of the epithelium. The OGF–OGFr pathway has been reported to be dysregulated in diabetic individuals and animal models, and is reflected in elevations of the inhibitory growth factor, OGF, chemically termed [Met5]-enkephalin. Recently, our laboratory reported elevated levels of OGF and OGFr in the serum and corneal epithelium of type 1 diabetic rats, suggesting that dysregulation of the OGF–OGFr axis may lead to dry eye, abnormal corneal surface sensitivity, and delayed re-epithelialization. Blockade of OGF–OGFr pathway using naltrexone, a potent opioid receptor antagonist, reverses dry eye symptoms and restores corneal surface sensitivity in diabetic rats when used as a therapy. Based on the evidence that both OGF and OGFr are elevated in type 1 diabetic rats, this study examined whether systemic or topical naltrexone treatment initiated at the time of induction of hyperglycemia could protect against the development of diabetic ocular surface complications. Diabetic male Sprague-Dawley rats treated systemically or topically with naltrexone had a delayed onset of dry eye and altered corneal surface sensitivity, and an improved healing rate for corneal wounds, that were comparable to non-diabetic rats. Serum levels of OGF were normal for rats receiving systemic naltrexone, and OGF tissue levels were normal for type 1 diabetic rats receiving twice daily naltrexone drops. OGFr levels remained elevated. These data support the role of the OGF–OGFr axis in regulation of ocular surface complications, and suggest that naltrexone therapy may be beneficial for pre-diabetic and early diabetic individuals.

C-Reactive protein and insulin growth factor 1 serum levels during the menstrual cycle in adolescents with Type 1 diabetes

2015 ◽  
Vol 33 (1) ◽  
pp. 70-76 ◽  
Author(s):  
E. Codner ◽  
P. M. Merino ◽  
D. Martínez ◽  
P. Lopez ◽  
C. Godoy ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Growth Factor ◽  
Menstrual Cycle ◽  
Serum Levels ◽  
C Reactive Protein ◽  
Insulin Growth Factor ◽  
Reactive Protein

scholarly journals Peripheral Neuropathy and Tear Film Dysfunction in Type 1 Diabetes Mellitus

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Stuti L. Misra ◽  
Dipika V. Patel ◽  
Charles N. J. McGhee ◽  
Monika Pradhan ◽  
Dean Kilfoyle ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Peripheral Neuropathy ◽  
Dry Eye ◽  
Ocular Surface ◽  
Tear Film ◽  
Lipid Layer ◽  
Film Stability ◽  
Tear Film Stability

Purpose.To compare tear film metrics in patients with type 1 diabetes mellitus (DM) and healthy controls and investigate the association between peripheral neuropathy and ocular surface quality.Methods.Dry eye symptoms were quantified in 53 patients with type 1 DM and 40 age-matched controls. Ocular examination included tear film lipid layer thickness grading, tear film stability and quantity measurement, and retinal photography. DM individuals additionally underwent a detailed neuropathy assessment.Results.Neither mean age nor dry eye symptom scores differed significantly between the DM and control groups (P=0.12andP=0.33, resp.). Tear lipid thickness (P=0.02), stability (P<0.0001), and quantity (P=0.01) were significantly lower in the DM group. Corneal sensitivity was also reduced in the DM group (P<0.001) and tear film stability was inversely associated with total neuropathy score (r=-0.29,P=0.03).Conclusion.The DM group exhibited significantly reduced tear film stability, secretion, and lipid layer quality relative to the age-matched control group. The negative correlation between tear film parameters and total neuropathy score suggests that ocular surface abnormalities occur in parallel with diabetic peripheral neuropathy.

scholarly journals Regulatory T-Cells Protect From Type 1 Diabetes After Induction by Coxsackievirus Infection in the Context of Transforming Growth Factor- 

Diabetes ◽  
2008 ◽  
Vol 57 (5) ◽  
pp. 1302-1311 ◽  
Author(s):  
M. J. Richer ◽  
N. Straka ◽  
D. Fang ◽  
I. Shanina ◽  
M. S. Horwitz
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Growth Factor ◽  
Regulatory T Cells ◽  
Transforming Growth Factor

Alterations of Tear Film and Ocular Surface in Children with Type 1 Diabetes Mellitus

2019 ◽  
Vol 28 (3) ◽  
pp. 362-369
Author(s):  
Merve Inanc ◽  
Hasan Kiziltoprak ◽  
Rumeysa Hekimoglu ◽  
Kemal Tekin ◽  
Servan Ozalkak ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Ocular Surface ◽  
Tear Film

scholarly journals Assessment of Serum Concentrations of Adropin, Afamin, and Neudesin in Children with Type 1 Diabetes

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Agnieszka Polkowska ◽  
Izabela Elżbieta Pasierowska ◽  
Marta Pasławska ◽  
Elżbieta Pawluczuk ◽  
Artur Bossowski
Keyword(s):  
Type 1 Diabetes ◽  
Glucose Metabolism ◽  
Statistical Significance ◽  
Serum Levels ◽  
Control Group ◽  
Diabetic Patients ◽  
Serum Concentrations ◽  
Novel Biomarkers ◽  
Varied Duration

Introduction. The increasing knowledge of adropin, afamin, and neudesin and the regulation of glucose metabolism and insulin resistance allows for the assessment of the differences in their concentrations between the groups with varied duration of diabetes mellitus (DM). Aim of the Study. Assessment of serum levels of adropin, afamin, and neudesin in children with type 1 diabetes, with respect to the disease duration. Materials and Methods. The study consisted of 138 patients aged 5–18 years (M 40.58%). Children with type 1 diabetes (n = 68) were compared to the control group (n = 70). The diabetic group was divided into 4 subgroups: (I) newly diagnosed patients, after an episode of ketoacidosis (n = 14), (II) duration no longer than 5 years (n = 18), (III) 5 to 10 years (n = 27), and (IV) longer than 10 years (n = 9). Serum concentrations of adropin, afamin, and neudesin were assessed and compared between the groups of patients. The criterion for statistical significance was p<0.05. Results. The concentrations of adropin and afamin across all subgroups were lower than that in the control group, while neudesin levels were higher in diabetic patients compared to the control group. The differences were statistically significant. Conclusions. Adropin, afamin, and neudesin may play a major role in the regulation of glucose metabolism and have a significant potential as novel biomarkers to predict future metabolic disorders. However, further multicentre studies on a larger cohort of patients are necessary to specify the role of these substances in the course and treatment of type 1 diabetes.

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