Inner Retinal Oxygen Delivery, Metabolism, and Extraction Fraction in Ins2Akita Diabetic Mice.
OBJECTIVE
Retinal nonperfusion and hypoxia are important factors in human diabetic retinopathy, and these presumably inhibit energy production and lead to cell death. The purpose of this study was to elucidate the effect of diabetes on inner retinal oxygen delivery and metabolism in a mouse model of diabetes.


METHODS
Phosphorescence lifetime and blood flow imaging were performed in spontaneously diabetic Ins2Akita (n = 22) and nondiabetic (n = 22) mice at 12 and 24 weeks of age to measure retinal arterial (O2A) and venous (O2V) oxygen contents and total retinal blood flow (F). Inner retinal oxygen delivery (DO2) and metabolism (MO2) were calculated as F ∗ O2A and F ∗ (O2A - O2V), respectively. Oxygen extraction fraction (OEF), which equals MO2/DO2, was calculated.


RESULTS
DO2 at 12 weeks were 112 ± 40 and 97 ± 29 nL O2/min in nondiabetic and diabetic mice, respectively (NS), and 148 ± 31 and 85 ± 37 nL O2/min at 24 weeks, respectively (P < 0.001). MO2 were 65 ± 31 and 66 ± 27 nL O2/min in nondiabetic and diabetic mice at 12 weeks, respectively, and 79 ± 14 and 54 ± 28 nL O2/min at 24 weeks, respectively (main effects = NS). At 12 weeks OEF were 0.57 ± 0.17 and 0.67 ± 0.09 in nondiabetic and diabetic mice, respectively, and 0.54 ± 0.07 and 0.63 ± 0.08 at 24 weeks, respectively (main effect of diabetes: P < 0.01).


CONCLUSIONS
Inner retinal MO2 was maintained in diabetic Akita mice indicating that elevation of the OEF adequately compensated for reduced DO2 and prevented oxidative metabolism from being limited by hypoxia.
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States.
Norman P
NP
Blair
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States.
Justin
J
Wanek
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States.
Anthony E
AE
Felder
Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, Illinois, United States.
Katherine C
KC
Brewer
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States 2Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, Illinois, United States 3University of Illinois Cancer Center, Population Health, Behavior, and Outcomes Program, Chicago, Illinois, United States.
Charlotte E
CE
Joslin
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States.
Mahnaz
M
Shahidi
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003930:Diabetic Retinopathy / Q000378:metabolism*; D000860:Hypoxia / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D012160:Retina / Q000378:metabolism*; D012171:Retinal Vessels / Q000502:physiology
D010100:Oxygen