1. The present review reports some of the earliest physiological chang
es that occur in the diabetic retina prior to any clinical or anatomic
al changes in an animal model of diabetes, 2. Using chemically induced
diabetes (by streptozotocin) in rats, retinal blood flow and vitreal
and retinal oxygen tension were determined after 5 weeks of sustained
hyperglycaemia, Blood flow was greater and was also redistributed in t
he diabetic group compared with values for the control group, At the s
ame time, oxygen tension distribution was altered around retinal arter
ioles, implying an increase in retinal oxygen consumption in these ear
ly diabetic retinas, 3. The possibility that the blood flow changes co
uld be due to altered control mechanisms in the retinal vasculature wa
s confirmed using an isolated, perfused eye preparation, In diabetic e
yes an altered reactivity to test pharmacological agents was demonstra
ted after 4 weeks of diabetes, 4, To further explore these vascular re
sponse changes we developed an isolated, perfused retinal arteriolar p
reparation in which individual segments of the vasculature can be test
ed, The possibility that insulin has a direct vasodilator effect on re
tinal arterioles was confirmed and was demonstrated to act via nitric
oxide released from the vascular endothelial cells, These data may imp
licate the diabetic-induced insulin changes in early retinal changes,
5, Evidence is presented that although early glucose control may be vi
tal in stopping the onset of diabetic retinopathy, there comes a stage
in the induced diabetic cascade where if the retinopathy has commence
d, good glucose control cannot stop the further progression of the ret
inopathy.