Abstract
BackgroundThe C57BLKS/J db/db (db/db) mouse is a widely used type 2 diabetic animal model, and this model develops early inner retinal neuronal dysfunction beginning at 24 weeks. The neural mechanisms that mediate early stage retinal dysfunction in this model are unknown. We evaluated visual response properties of retinal ganglion cells (RGCs) during the early stage of diabetic insult (8, 12, and 20 wk) in db/db mice and determined if increased oxidative stress plays a role in impaired visual functions of RGCs in 20 wk old db/db mice.Methodology/Principal Findings In vitro extracellular single-unit recordings from RGCs in wholemount retinas were performed. The receptive field size, luminance threshold, and contrast gain of the RGCs were investigated. Although ON- and OFF-RGCs showed a different time course of RF size reduction, by 20 wk, the RF of ON- and OFF-RGCs were similarly affected. The LT of ON-RGCs was significantly elevated in 12 and 20 wk db/db mice compared to the LT of OFF-RGCs. The diabetic injury also affected contrast gains of ON- and OFF-RGCs differently. The generation of reactive oxidative species (ROS) in fresh retina was estimated by dihydroethidium. Superoxide dismutase (SOD) (300 unit/ml) was applied in Ames medium to the retina, and visual responses of RGCs were recorded for five hours. ROS generation in the retinas of db/db mice increased at 8wk and continued to progress at 20 wk of ages. In vitro application of SOD improved visual functions in 20 wk db/db mice but the SOD treatment affected ON- and OFF-RGCs differently in db/m retina.Conclusions/SignificanceThe altered visual functions of RGCs were characterized by the reduced RF center size, elevated LT, and attenuated contrast gain in 12 and 20 wk db/db mice, respectively. These altered visual functions could, at least partly, be due to oxidative stress since in vitro application of SOD effectively improves visual functions.
Highlights
Diabetic retinopathy (DR) is classically thought of as a microvascular disease of the retinal capillaries
Visual response properties of ON- and OFF-retinal ganglion cells (RGCs) were analyzed. It was followed by detecting intracellular reactive oxidative species (ROS) levels in db/db and db/m mice retina, and we evaluated the effect of Superoxide dismutase (SOD) on the visual functions of RGCs in 20 wk db/db mice
This study demonstrates that the declination of the visual response properties of RGCs, including receptive field (RF) size, luminance response, and contrast gain in db/db mice
Summary
Diabetic retinopathy (DR) is classically thought of as a microvascular disease of the retinal capillaries. Different types of retinal neuronal deficits have been reported in diabetic animal models prior to the onset of vascular compromise including alterations of photoreceptor [9,10,11,12], bipolar [13,14], amacrine [15,16] and ganglion cell [17,18,19,20] function. Neural mechanisms that mediate early stage diabetic retinal dysfunction remain to be determined. We evaluated visual response properties of retinal ganglion cells (RGCs) during the early stage of diabetic insult (8, 12, and 20 wk) in db/db mice and determined if increased oxidative stress plays a role in impaired visual functions of RGCs in 20 wk old db/db mice
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