Abstract
Purpose :
Inflammation has a potential role in the initial stages of diabetic retinopathy and part of the ischemia/reperfusion-induced retinal damage. The potent anti-inflammatory neuropeptide α-MSH helps to maintain a healthy ocular environment and retinal cell survival. We studied the possibility that α-MSH anti-inflammatory therapy can reduce damage associated with retina ischemia/reperfusion (I/R).
Methods :
Ischemia was induced by cannulation of healthy C57BL/6 mouse ocular anterior chamber and raising the intraocular pressure (IOP) to 90-100 mmHg for 90 minutes. The cannula was removed and IOP allowed to return to normal for reperfusion. Mice were given an intraperitoneal injection of 5μg of α-MSH. After 2 or 7 days the eyes were enucleated, fixed, and embedded in paraffin for sectioning. The sections were stained with hematoxylin and eosin, and imaged. Sections were scored for the extent of infiltration, retinal folding, and retinal layer loss to describe the degree of retinal damage. Also, the retinal ganglion cells were counted over three sequential sections. The number of ganglion cells per mm length of retina was calculated.
Results :
Visual analysis of the retinal sections shows a noticeable loss of ganglion cells and retinal layers in the untreated mice that becomes severe with time and it is lessened by α-MSH treatment. The distinction between untreated and treated is largely from an increase in retinal folding and immune cell infiltration in the untreated mice. There was a significant reduction in the disease scores at day 2 between α-MSH treated (0.9 ± 0.65) and untreated mice (2.25 ± 0.96) (P<0.05). Untreated mice had significantly fewer ganglion cells on day 2 (43 ± 9 cells/mm) and 7 (28 ± 4 cells/mm) than healthy mice (78 ± 5 cells/mm). On day 2, α-MSH treated mice had significantly more ganglion cells (63 ± 14 cells/mm, P=0.02) than untreated mice and were not significantly distinct from healthy mice. However, ganglion cell survival was not significantly higher in the α-MSH treated mice on day 7 (40 ± 14 cells/mm) compared to the untreated mice.
Conclusions :
The retinal damage caused by I/R was significantly reduced by α-MSH therapy. The results suggest that there is a role of inflammation early in diabetic retinopathy that if suppressed can minimize damage.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.