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Robert A Linsenmeier, Desmond Henderson, Andrey V Dmitriev; Intraretinal oxygen measurements in rats with six to twelve months of diabetes. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2715.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate whether the rat retina exhibits lower PO2 in the inner retina as diabetes progresses.
Long-Evans rats were made diabetic with IP streptozotocin in citrate buffer, and were maintained under poor control with plasma glucose of at least 500 mg/dl for 6 to 12 months. Age-matched control animals were treated only with buffer. Animals were then anesthetized and oxygen microelectrode penetrations were made through the retina in order to measure intraretinal PO2 and the local electroretinogram in a terminal experiment. Arterial PO2 was between 90 and 115 mmHg in all cases. ERGs were also measured in the vitreous humor. Eyes were fixed and flat mounted, and ganglion cells were labeled with Brn3A and/or Brn 3B antibody and counted.
Previous work showed that PO2 in the inner retina was higher in diabetic rats than control rats at 3 months. In 6 and 9-12 month animals, PO2 was measured in as many locations as possible during dark adaptation. To avoid possible errors due to inaccuracies in electrode calibration, the PO2 averaged over the inner half of the retina (PIR) was normalized to the PO2 measured in the same profile in the choriocapillaris (Pc). PIR/Pc was averaged across profiles in an animal, and then across animals. The PIR/Pc ratio was was between 0.44 and 0.47 in all four groups: 6 month and 9-12 month diabetics and controls (n=26 animals total). Neither Pc nor PIR/Pc was different in diabetics and controls. Averaging could miss some changes, but if the retina were hypoxic due to capillary plugging or capillary loss, it would also be expected that some profiles in diabetics would not show the peaks in PO2 caused by capillary sources of oxygen, which are typical in the normal retina of animals with a retinal circulation. Profiles from diabetics and controls were indistinguishable in this respect. However, diabetics had large progressive changes in both the b- and c-waves of the ERG, and had reduced ganglion cell numbers by 6 months.
While there could be small areas of hypoxia in rats with up to one year of diabetes, it was not possible to demonstrate this with either average values of inner retinal PO2 or inspection of individual profiles. The loss of ganglion cells suggests that the oxygen utilization decreases with time, and the constancy of PO2 then implies that the flow in the retinal circulation can still regulating to keep PO2 at normal levels.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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