Inner Retinal Oxygen Delivery, Metabolism, and Extraction Fraction in Ins2 ^Akita Diabetic Mice

Abstract

PurposeRetinal 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.MethodsPhosphorescence 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.ResultsDO2 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).ConclusionsInner 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.

Imaging single-cell blood flow in the smallest to largest vessels in the living retina

“…In particular, about half of the studies, which use intravital microscopy, report vessels diameters that are ~2 times greater, mean velocities that are ~2 times greater and mean flow rates that are ~8 times greater than that of all other techniques, including our own (Figure 11). Our values of mean diameter of primary vessels matches that of the in vivo slit lamp biomicroscope study (Blair et al, 2016) and is within the range reported by ex vivo scanning electron microscopy (Ninomiya and Inomata, 2006). Our values of mean flow rate matches that reported by en face Doppler OCT/OMAG studies (Zhi et al, 2014; Zhi et al, 2012).…”

“…While investigating the mouse literature for normative values of diameter, velocity and flow in retinal vessels, we found, first, that there is a paucity of such studies. To the best of our knowledge, we have counted all of 15 journal papers which measure retinal blood velocity and/or flow in the living mouse eye (Blair et al, 2016; Harris et al, 2013; Lee and Harris, 2008; Liu et al, 2017; Muir et al, 2012; Wang et al, 2010; Wang et al, 2011; Watts et al, 2013; Wright and Harris, 2008; Wright et al, 2009; Wright et al, 2012; Yadav and Harris, 2011; Zawadzki et al, 2015; Zhi et al, 2014; Zhi et al, 2012). As stated earlier, all these studies measure velocity/flow only in the primary (first generation) vessels emerging from the optic disk.…”

Imaging single-cell blood flow in the smallest to largest vessels in the living retina

“…In particular, about half of the studies, which use intravital microscopy, report vessels diameters that are ~2 times greater, mean velocities that are ~2 times greater and mean flow rates that are ~8 times greater than that of all other techniques, including our own (Figure 11). Our values of mean diameter of primary vessels matches that of the in vivo slit lamp biomicroscope study (Blair et al, 2016) and is within the range reported by ex vivo scanning electron microscopy (Ninomiya and Inomata, 2006). Our values of mean flow rate matches that reported by en face Doppler OCT/OMAG studies (Zhi et al, 2014; Zhi et al, 2012).…”

“…While investigating the mouse literature for normative values of diameter, velocity and flow in retinal vessels, we found, first, that there is a paucity of such studies. To the best of our knowledge, we have counted all of 15 journal papers which measure retinal blood velocity and/or flow in the living mouse eye (Blair et al, 2016; Harris et al, 2013; Lee and Harris, 2008; Liu et al, 2017; Muir et al, 2012; Wang et al, 2010; Wang et al, 2011; Watts et al, 2013; Wright and Harris, 2008; Wright et al, 2009; Wright et al, 2012; Yadav and Harris, 2011; Zawadzki et al, 2015; Zhi et al, 2014; Zhi et al, 2012). As stated earlier, all these studies measure velocity/flow only in the primary (first generation) vessels emerging from the optic disk.…”

Imaging Single–Cell Blood Flow in the Smallest to Largest Vessels in the Living Retina

“…A graphical summary, classified by imaging technique, is given in Figure 11. Our value of mean diameter of primary vessels matches that of the in vivo slit lamp biomicroscope (Blair et al, 2016) study and is within the range reported by ex vivo scanning electron microscopy (Ninomiya & Inomata, 2006). However, the diameters reported by intravital microscopy studies (Harris et al, 2013; Lee & Harris, 2008; Z.…”

Age-Related Decline of Retinal Oxygen Extraction in Healthy Subjects

“…Microelectrode measurements provide local values of retinal oxygen tension only. 45,46 Phosphorescence quenching measures retinal oxygen tension in retinal vessels, 56,57 and direct comparison with oxygen saturation measurements as obtained in the present study may be difficult. However, there are several studies indicating that the technique provides sufficiently valid measurements.…”

Imaging single-cell blood flow in the smallest to largest vessels in the living retina

“…In particular, about half of the studies, which use intravital microscopy, report vessels diameters that are ~2 times greater, mean velocities that are ~2 times greater and mean flow rates that are ~8 times greater than that of all other techniques, including our own (Figure 11). Our values of mean diameter of primary vessels matches that of the in vivo slit lamp biomicroscope study (Blair et al, 2016) and is within the range reported by ex vivo scanning electron microscopy (Ninomiya and Inomata, 2006). Our values of mean flow rate matches that reported by en face Doppler OCT/OMAG studies (Zhi et al, 2014; Zhi et al, 2012).…”

“…While investigating the mouse literature for normative values of diameter, velocity and flow in retinal vessels, we found, first, that there is a paucity of such studies. To the best of our knowledge, we have counted all of 15 journal papers which measure retinal blood velocity and/or flow in the living mouse eye (Blair et al, 2016; Harris et al, 2013; Lee and Harris, 2008; Liu et al, 2017; Muir et al, 2012; Wang et al, 2010; Wang et al, 2011; Watts et al, 2013; Wright and Harris, 2008; Wright et al, 2009; Wright et al, 2012; Yadav and Harris, 2011; Zawadzki et al, 2015; Zhi et al, 2014; Zhi et al, 2012). As stated earlier, all these studies measure velocity/flow only in the primary (first generation) vessels emerging from the optic disk.…”

Imaging Single–Cell Blood Flow in the Smallest to Largest Vessels in the Living Retina

“…A graphical summary, classified by imaging technique, is given in Figure 11. Our value of mean diameter of primary vessels matches that of the in vivo slit lamp biomicroscope (Blair et al, 2016) study and is within the range reported by ex vivo scanning electron microscopy (Ninomiya & Inomata, 2006). However, the diameters reported by intravital microscopy studies (Harris et al, 2013; Lee & Harris, 2008; Z.…”

Age-Related Decline of Retinal Oxygen Extraction in Healthy Subjects

“…Microelectrode measurements provide local values of retinal oxygen tension only. 45,46 Phosphorescence quenching measures retinal oxygen tension in retinal vessels, 56,57 and direct comparison with oxygen saturation measurements as obtained in the present study may be difficult. However, there are several studies indicating that the technique provides sufficiently valid measurements.…”

Imaging single-cell blood flow in the smallest to largest vessels in the living retina

“…In particular, about half of the studies, which use intravital microscopy, report vessels diameters that are ~2 times greater, mean velocities that are ~2 times greater and mean flow rates that are ~8 times greater than that of all other techniques, including our own (Figure 11). Our values of mean diameter of primary vessels matches that of the in vivo slit lamp biomicroscope study (Blair et al, 2016) and is within the range reported by ex vivo scanning electron microscopy (Ninomiya and Inomata, 2006). Our values of mean flow rate matches that reported by en face Doppler OCT/OMAG studies (Zhi et al, 2014; Zhi et al, 2012).…”

“…While investigating the mouse literature for normative values of diameter, velocity and flow in retinal vessels, we found, first, that there is a paucity of such studies. To the best of our knowledge, we have counted all of 15 journal papers which measure retinal blood velocity and/or flow in the living mouse eye (Blair et al, 2016; Harris et al, 2013; Lee and Harris, 2008; Liu et al, 2017; Muir et al, 2012; Wang et al, 2010; Wang et al, 2011; Watts et al, 2013; Wright and Harris, 2008; Wright et al, 2009; Wright et al, 2012; Yadav and Harris, 2011; Zawadzki et al, 2015; Zhi et al, 2014; Zhi et al, 2012). As stated earlier, all these studies measure velocity/flow only in the primary (first generation) vessels emerging from the optic disk.…”

Imaging Single–Cell Blood Flow in the Smallest to Largest Vessels in the Living Retina

“…A graphical summary, classified by imaging technique, is given in Figure 11. Our value of mean diameter of primary vessels matches that of the in vivo slit lamp biomicroscope (Blair et al, 2016) study and is within the range reported by ex vivo scanning electron microscopy (Ninomiya & Inomata, 2006). However, the diameters reported by intravital microscopy studies (Harris et al, 2013; Lee & Harris, 2008; Z.…”

Age-Related Decline of Retinal Oxygen Extraction in Healthy Subjects

“…Microelectrode measurements provide local values of retinal oxygen tension only. 45,46 Phosphorescence quenching measures retinal oxygen tension in retinal vessels, 56,57 and direct comparison with oxygen saturation measurements as obtained in the present study may be difficult. However, there are several studies indicating that the technique provides sufficiently valid measurements.…”