Retinal hypoxia in long-term diabetic cats.
OBJECTIVE
To determine whether the retina is hypoxic in early stages of diabetic retinopathy in cats and to correlate intraretinal PO2 with fluorescein angiographic and histologic alterations.


METHODS
Intraretinal PO2 was measured with microelectrodes in three cats with long-standing diabetes (>6 years) that had been followed with fluorescein angiographs every 6 months. Average PO2 in the inner vascularized half of the retina was compared with similar measurements in 21 control animals. Photoreceptor oxygen consumption was also compared. The retinal vascular endothelium of the diabetic animals was stained for ADPase activity in flatmounts, and transverse sections were used to visualize microscopic alterations in vascular structure.


RESULTS
PO2 in the inner half of the retina was abnormally low in the diabetic cats, 7.7+/-5.2 mm Hg (35 penetrations in 3 cats) versus 16.4+/-9.3 mm Hg in normal cats (85 penetrations in 21 cats) (P << 0.001). Oxygenation was almost normal in some regions of the diabetic retinas, but little evidence of oxygen supply from the retinal circulation was observed in other regions. Inner retinal hypoxia was present in areas with no detectable capillary dropout in fluorescein angiograms or flatmounts. The worst changes histologically were microaneurysms, leukocyte and platelet plugging of aneurysms and venules, and degenerating endothelial cells in capillary walls. These histologic abnormalities were confined to small regions, some of which could be positively correlated with markedly abnormal PO2 profiles. Photoreceptor oxygen utilization was not affected in two diabetic cats, but was below normal in one animal in which choroidal PO2 was low.


CONCLUSIONS
This is the first direct demonstration of retinal hypoxia in early diabetic retinopathy, before capillary dropout was evident clinically. Hypoxia was correlated with endothelial cell death, leukocyte plugging of vessels, and microaneurysms.
Department of Biomedical Engineering, Northwestern University, Evanston, Illinois 60208-3107, USA.
R A
RA
Linsenmeier
R D
RD
Braun
M A
MA
McRipley
L B
LB
Padnick
J
J
Ahmed
D L
DL
Hatchell
D S
DS
McLeod
G A
GA
Lutty
D000818:Animals; D001081:Apyrase / Q000378:metabolism; D002415:Cats; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000201:enzymology / Q000473:pathology; D005451:Fluorescein Angiography; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008839:Microelectrodes; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption; D010180:Pancreatectomy / Q000009:adverse effects; D010786:Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D012171:Retinal Vessels / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
D001081:Apyrase; D010100:Oxygen