Inner Retinal Oxygen Metabolism and Delivery in Streptozotocin Diabetic Rats

Abstract

Purpose: Diabetic retinopathy is a vision threatening disease causing alterations in the retinal vasculature that likely impair the supply and utilization of oxygen. The purpose of this study is to report for the first time measurements of inner retinal oxygen metabolism (MO₂) and delivery (DO₂) by combined oxygen tension (PO₂) and blood flow imaging in a streptozotocin (STZ) rat model of diabetes.

Methods: Imaging was performed in diabetic rats (N = 8) four weeks after intravenous injection of STZ (60 mg/kg) and in healthy control rats (N = 10). PO₂ in all major retinal arteries and veins was measured using a previously established phosphorescence lifetime imaging system and converted to arterial (O_2A) and venous (O_2V) oxygen contents, respectively. Blood velocity was determined by imaging the intravascular motion of fluorescent microspheres and venous diameter was measured from red-free retinal images, allowing calculation of blood flow in each vein. Total retinal venous blood flow (F) was determined by summing blood flows in all veins. Inner retinal MO₂ was assessed based on the product of F and the arteriovenous oxygen content difference and DO₂ was calculated from the product of F and O_2A, based on Fick’s principle. Unpaired Student’s t-test and ANCOVA that adjusted for variability due to DO₂ were used for statistical comparison.

Results: Rats injected with STZ had blood glucose levels of 398 ± 56 mg/dL, confirming the presence of diabetes. As compared to control rats, O_2A in diabetic rats was similar (p = 0.2) and O_2V was significantly higher (p = 0.02). The arteriovenous oxygen content difference and F were not significantly different between diabetic and control rats (p ≥ 0.3). Inner retinal DO₂ in diabetic (1011 ± 193 nL O₂/min) and control (941 ± 231 nL O₂/min) rats were comparable (p = 0.5). Likewise, inner retinal MO₂ in diabetic (442 ± 62 nL O₂/min) and control (516 ± 175 nL O₂/min) rats were similar (p = 0.3). After adjusting for variability due to DO₂, MO₂ was significantly lower in diabetic rats as compared to control rats (p = 0.03).

Conclusions: For given levels of oxygen delivery, a significant reduction in inner retinal MO₂ was established in diabetic rats, suggesting alterations in the retinal energy metabolism early in the disease progression.

Keywords: 551 imaging/image analysis: non-clinical • 635 oxygen • 499 diabetic retinopathy