Protective effects of Growth Hormone Releasing Hormone (GHRH) agonism in the diabetic retina

Abstract

 

Purpose

 

The hypothalamic hormone GHRH has been shown to possess extrapituitary activities including neuroimmune and neuroprotective functions. We have previously shown that GHRH receptors are present in retinas of human and rodents and are mainly localized on retinal ganglion cells. Here we have explored the protective effects of the GHRH agonist JI-34 in the diabetic retina.

 

Methods

 

Streptozotocin-induced diabetic rats (STZ-rats) were kept diabetic for 6 weeks. One group of STZ-rats was also treated with 5μg/kg of the GHRH agonist JI-34 which was injected sub-cutaneously every other day starting one week after the induction of hyperglycemia and continued for the duration of diabetes. Immunohistochemical and Western analyses were conducted to assess the expression levels of GHRH-R, Intercellular adhesion molecule-1 (ICAM-1), Glial Fibrillary Acidic Protein (GFAP) and Vascular Endothelial Growth Factor (VEGF). Scotopic electroretinographic analysis was performed to assess neuroretinal function.

 

Results

 

Treatments of STZ-rats with JI-34 had no effect on blood glucose levels nor affected body weight changes with progression of diabetes. However, JI-34 treatments significantly reduced the expression levels of ICAM-1, GFAP and VEGF in the diabetic retina. In addition, we observed a strong up-regulation of GHRH-R expression in retinal ganglion cells of STZ-rats which resulted in a more evidenced neurofibrillary layer. These effects were associated with improved scotopic electroretinographic responses in STZ-rats treated with JI-34.

 

Conclusions

 

Our data show that the GHRH agonist JI-34 possesses protective effects in the diabetic retina by down-regulating inflammatory mediators and promoting neuroprotective responses probably involving preservation of ganglion cells activity and survival.

 

Keywords: 499 diabetic retinopathy • 615 neuroprotection