Abstract
Purpose :
Diabetic retinopathy caused by Type II diabetes is the leading cause of blindness in working-age population. Our previous study indicated that α-Melanocyte-stimulating hormone (α-MSH) possesses retinal protective effects in streptozocin induced diabetic retinopathy. In this study, we seek to use the db mouse model to study the protective effects of α-MSH against the retinal damage caused by Type II diabetes.
Methods :
Forty BKS-db (-/-) mice at 9 w of age were randomly divided into normal saline and α-MSH groups. In addition, 20 BKS-db (+/-) mice (9 w of age) were included as a control group. In w 10 and 12 of age, α-MSH (3.3 μg/μl, 1 μl/eye) were intravitreally injected into the corresponding group of mice; whereas the control group was injected with equal volume of saline. The electroretinography (ERG) was examined at 15 w of age. The eyeballs were enucleated 2 days later for histology and immunohistochemistry. The thicknesses of retinal layers were measured and glial fibrillary acidic protein (GFAP) was detected by immunohistochemistry. Additionally, the oxidative stress and apoptotic conditions were examined by dihydroethidium (DHE) and TUNEL staining, respectively.
Results :
The ERG results showed that, when stimulated with 0.01 cd*s/m2 lights, the implicit times of both a wave and b wave of the BKS-db (-/-) mice were significantly prolonged, and the b wave amplitude reduced as compared to those of the controls (all P < 0.05); additionally, the a wave amplitude of the mutants under the stimuli of 30 cd*s/m2 was also significantly lower than the controls (P < 0.05), while all these retinal dysfunctions were restored by α-MSH. Furthermore, the thicknesses of inner nuclear layer and total retina were significantly reduced in the mutants in comparison to the controls, which were improved by α-MSH. Finally, the staining intensities of GFAP, DHE, and TUNEL-positive signals were significantly elevated in the db retinas compared to those in the controls (all P < 0.001); whereas all of these abnormalities were significantly alleviated or rectified by α-MSH.
Conclusions :
Intravitreal injections of α-MSH partially restore retinal structure and functions of Type II diabetes. The molecular mechanism underlying the α-MSH's protective effects deserves further investigation.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.