Retinal protective effects of lutein and candesartan against neurodegeneration and inflammation in diabetic retinopathy using the hyperglycemic InsAkita/+ mouse model

Abstract

Purpose : We previously showed that lutein is neuroprotective after retinal ischemia/reperfusion injury in normal mice while candesartan can restore retinal function in hyperglycemic InsAkita/+ mice. Here, we aimed to investigate the effects of lutein (a naturally occurring xanthophyll) and candesartan (an angiotensin receptor antagonist) co-treatment on retinal function and morphology in early non-proliferative diabetic retinopathy using the InsAkita/+ mouse model.

Methods : Six-week old male InsAkita/+mice were subjected to the following treatments: 26 weeks (vehicle; 0.01cc candesartan + 4.2cc lutein; 0.1cc candesartan + 4.2cc lutein) 36 weeks (vehicle; 0.01cc candesartan + 4.2cc lutein; 0.1cc candesartan + 4.2cc lutein; 0.1cc candesartan)

Retinal paraffin sections (5um) were stained with haematoxylin and eosin for histological examination. Thickness of each retinal layer was measured at central (200um from optic nerve head), peripheral (200um from retinal periphery) and mid-peripheral (midpoint between central and peripheral reference points) retina. Total number of viable cells in ganglion cell layer (GCL) was counted.

Results : Compared with their respective vehicle-treated groups, retina in drug treatment groups were generally thicker. At 26 weeks, 0.01cc candesartan + lutein co-treatment group showed a thicker inner nuclear layer (INL) in central and mid-peripheral regions while 0.1cc group showed a thicker INL in central and peripheral regions. At 36 weeks, 0.1cc candesartan + lutein co-treatment group showed a thicker outer nuclear layer (ONL) in central and mid-peripheral regions whereas 0.1cc candesartan single treatment group shows an even thicker ONL together with a thicker inner plexiform layer (IPL). The thicker retinal layers were possibly due to a reduction in cell loss since the difference was concentrated on the nuclear layers. This was supported by the results of retinal cell count as all treatment groups showed more viable cells in GCL than that in vehicle-treated groups. Yet, 0.1cc candesartan single treatment may increase retinal edema resulting in a thicker IPL despite having a greater effect in reducing cell loss.

Conclusions : Lutein and candesartan co-treatment exerts retinal protective effect by reducing cell loss in early non-proliferative diabetic retinopathy.