Drug intervention can correct subnormal retinal oxygenation response in experimental diabetic retinopathy.
OBJECTIVE
Early subnormal retinal oxygenation response to a hyperoxic provocation (DeltaPo2) is strongly associated with subsequent experimental diabetic retinopathy and can be reversed by drug treatments started with the induction of diabetes. It is not yet known whether drug treatment can reverse an established subnormal DeltaPo2.


METHODS
Retinal DeltaPo2 was measured in two separate experimental paradigms in streptozotocin-induced diabetic rats. In a prevention study, measurements were performed in untreated diabetic rats, 3 months after the initiation of hyperglycemia (D3mo), in age-matched nondiabetic rats (C3mo), and in diabetic rats treated orally for 3 months with celecoxib, a cyclooxygenase (COX)-2-selective inhibitor, (D3mo+COX2i). In an intervention study, measurements were performed in untreated diabetic rats 4 months after the initiation of diabetes (D4mo), in age-matched nondiabetic rats (C4mo), and in diabetic rats that were untreated for 3 months and then were orally treated for an additional month with either celecoxib (D4mo+COX2i) or l-N (6)-(1-iminoethyl)lysine 5-tetrazole amide, a prodrug of an inhibitor of inducible nitric oxide synthase (iNOS, D4mo+ iNOSi).


RESULTS
In the prevention arm, subnormal (P < 0.05) retinal DeltaPo2 was found in the D3mo group, but not in the D3mo+COX2i group (P > 0.05). In a previous study, it was reported that retinal DeltaPo2 also corrected in a D3mo+iNOSi group. In the intervention arm, retinal DeltaPo2 levels in the D4mo and D4mo+iNOSi, but not the D4mo+COX2i, groups were (P < 0.05) subnormal.


CONCLUSIONS
These results demonstrate, for the first time, that drug treatment can reverse an established subnormal DeltaPo2. Furthermore, this effect could not be predicted by a drugs' ability to prevent the development of subnormal DeltaPo2.
Berkowitz
Bruce A
BA
Department of Anatomy and Cell Biology, Wayne State University, Detroit, MI 48201, USA. baberko@med.wayne.edu
Roberts
Robin
R
Luan
Hongmei
H
Peysakhov
Jamie
J
Knoerzer
Deborah L
DL
Connor
Jane R
JR
Hohman
Thomas C
TC
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002245:Carbon Dioxide / Q000008:administration & dosage; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology / Q000517:prevention & control*; D003930:Diabetic Retinopathy / Q000503:physiopathology / Q000517:prevention & control*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D008239:Lysine / Q000031:analogs & derivatives / Q000627:therapeutic use; D008279:Magnetic Resonance Imaging; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052247:Nitric Oxide Synthase Type II; D010100:Oxygen / Q000008:administration & dosage / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects* / Q000502:physiology; D010313:Partial Pressure; D011720:Pyrazoles / Q000627:therapeutic use; D051381:Rats; D012160:Retina / Q000187:drug effects* / Q000503:physiopathology; D013449:Sulfonamides / Q000627:therapeutic use
D001786:Blood Glucose; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; C090663:N(6)-(1-iminoethyl)lysine; D011720:Pyrazoles; D013449:Sulfonamides; D002245:Carbon Dioxide; C011700:carbogen; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D000068579:Celecoxib; D008239:Lysine; D010100:Oxygen