Vascular and electroretinogram responses to hypercapnia and hyperoxia in the Streptozotocin diabetic rat

Abstract

Purpose : To investigate the effect of O₂ and CO₂ inhalation (hyperoxia and hypercapnia) on retinal blood vessel calibre and inner retinal function at early stages in the streptozotocin (STZ) model of diabetes.

Methods : Dark Agouti rats aged 8 weeks received intravenous STZ (55mg/Kg, n = 10) or vehicle injection (citrate buffer, n=10). After 4 weeks, Electroretinogram (ERG) and fundus imaging were conducted under general anaesthesia (60:5 mg/Kg Ketamine: Xylazine).
100% O₂ and CO₂ mix (10% CO₂ / 90% room air) were delivered in randomised order for 5min, followed by 5 min recovery. Arterial blood gas was taken to verify hyperoxia and hypercapnia. Retinal vessels were imaged every 10 seconds and analysed using ImageJ (percentage relative to baseline). The scotopic threshold response (STR, -5.01 logcd.s/m²) was recorded every minute during the protocol.

Results : STZ animals developed hyperglycemia compared to controls (25±0.8 vs 7.7±0.3mmol/L, p<0.05). CO₂ produced similar hypercapnia between STZ and control animals (PaCO₂ +8.0±2.1mmHg vs +10.4±8.0mmHg, p=0.44), but more vasodilation in STZ animals (arteriole 113±1%, venule 112±1%) compared to controls (arteriole 109±6%, venule 109±2%, p<0.01). Arterioles in STZ animals remained dilated for the duration of hypercapnia, while control arteries reconstricted after 2 minutes. O₂ produced hyperoxia similarly between the STZ and control groups (PaO2 +254±34 vs (+263±38mmHg, p=0.85) with no difference in vasoconstriction magnitude (STZ arteriole 86±1%; venule 85±1%; control arteriole 87±2%, vein 86±2%, p=0.67). Despite this, STZ animals showed slower venule vasoconstriction during hyperoxia. Hypercapnia produced similar increases in pSTR (Cit 144±13%, STZ 152±16% P=0.49) and nSTR amplitude (Cit 49±12%, STZ 53±11% P=0.89) in both groups of animals. Hyperoxia produced significantly more reduction in pSTR (Cit 90±4%, STZ 81±6% P< 0.01), and significantly more increase in nSTR (Cit 117%±5%, STZ 125±12% P=0.03) in STZ animals compared to citrate controls.

Conclusions : Hypercapnia and hyperoxia produce robust vasodilation and vasoconstriction respectively. Vasodilation is associated with reduction in nSTR and therefore increased pSTR. Vasoconstriction produces a larger nSTR and smaller pSTR. This effect was exaggerated in diabetic animals and may reflect disconnect in the timecourse between arteriole and venule vasoconstriction in STZ rats.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.