scholarly journals Protective effects of agonists of growth hormone-releasing hormone (GHRH) in early experimental diabetic retinopathy

2017 ◽  
Vol 114 (50) ◽  
pp. 13248-13253 ◽  
Author(s):  
Menaka C. Thounaojam ◽  
Folami L. Powell ◽  
Sagar Patel ◽  
Diana R. Gutsaeva ◽  
Amany Tawfik ◽  
...  

The potential therapeutic effects of agonistic analogs of growth hormone-releasing hormone (GHRH) and their mechanism of action were investigated in diabetic retinopathy (DR). Streptozotocin-induced diabetic rats (STZ-rats) were treated with 15 μg/kg GHRH agonist, MR-409, or GHRH antagonist, MIA-602. At the end of treatment, morphological and biochemical analyses assessed the effects of these compounds on retinal neurovascular injury induced by hyperglycemia. The expression levels of GHRH and its receptor (GHRH-R) measured by qPCR and Western blotting were significantly down-regulated in retinas of STZ-rats and in human diabetic retinas (postmortem) compared with their respective controls. Treatment of STZ-rats with the GHRH agonist, MR-409, prevented retinal morphological alteration induced by hyperglycemia, particularly preserving survival of retinal ganglion cells. The reverse, using the GHRH antagonist, MIA-602, resulted in worsening of retinal morphology and a significant alteration of the outer retinal layer. Explaining these results, we have found that MR-409 exerted antioxidant and anti-inflammatory effects in retinas of the treated rats, as shown by up-regulation of NRF-2-dependent gene expression and down-regulation of proinflammatory cytokines and adhesion molecules. MR-409 also significantly down-regulated the expression of vascular endothelial growth factor while increasing that of pigment epithelium-derived factor in diabetic retinas. These effects correlated with decreased vascular permeability. In summary, our findings suggest a neurovascular protective effect of GHRH analogs during the early stage of diabetic retinopathy through their antioxidant and anti-inflammatory properties.

Author(s):  
A. D. Rogol ◽  
R. M. Blizzard ◽  
P. M. Martha ◽  
W. S. Evans ◽  
M. L. Vance ◽  
...  

Diabetes ◽  
1987 ◽  
Vol 36 (2) ◽  
pp. 159-162 ◽  
Author(s):  
P. Pietschmann ◽  
G. Schernthaner ◽  
F. Prskavec ◽  
C. Gisinger ◽  
H. Freyler

Diabetes ◽  
1987 ◽  
Vol 36 (2) ◽  
pp. 159-162 ◽  
Author(s):  
P. Pietschmann ◽  
G. Schernthaner ◽  
F. Prskavec ◽  
C. Gisinger ◽  
H. Freyler

Author(s):  
Eva Horvath ◽  
Kalman Kovacs ◽  
B. W. Scheithauer ◽  
R. V. Lloyd ◽  
H. S. Smyth

The association of a pituitary adenoma with nervous tissue consisting of neuron-like cells and neuropil is a rare abnormality. In the majority of cases, the pituitary tumor is a chromophobic adenoma, accompanied by acromegaly. Histology reveals widely variable proportions of endocrine and nervous tissue in alternating or intermingled patterns. The lesion is perceived as a composite one consisting of two histogenetically distinct parts. It has been suggested that the neuronal component, morphologically similar to secretory neurons of the hypothalamus, may initiate adenoma formation by releasing stimulatory substances. Immunoreactivity for growth hormone releasing hormone (GRH) in the neuronal component of some cases supported this view, whereas other findings such as consistent lack of growth hormone (GH) cell hyperplasia in the lesions called for alternative explanation.Fifteen tumors consisting of a pituitary adenoma and a neuronal component have been collected over a 20 yr. period. Acromegaly was present in 11 patients, was equivocal in one, and absent in 3.


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