Prevention of retinal capillary basement membrane thickening in diabetic dogs by a non-steroidal anti-inflammatory drug.
OBJECTIVE
To investigate the effect of treatment with the non-steroidal anti-inflammatory drug Sulindac on the early vascular pathology of diabetic retinopathy in the dog, and it's effect on recognised biochemical indices of hyperglycaemia-related pathophysiology.


METHODS
Experimental diabetes (streptozotocin/alloxan) was induced in 22 male beagle dogs and 12 of the animals were assigned at random to receive oral Sulindac (10 mg/kg daily). Age- and sex-matched control animals were maintained as non-diabetic controls. After 4 years, several morphological parameters were quantified in the retinal microvasculature of each animal group using an established stereological method. Also, the following diabetes-associated biochemical parameters were analysed: accumulation of advanced glycation end products (AGEs), red blood cell polyol levels and antioxidant status.


RESULTS
Diabetes increased red blood cell sorbitol levels when compared to non-diabetic controls (p< or =0.05), however, there was no difference in sorbitol levels between the untreated and the treated diabetic animals. No significant differences were found in red blood cell myoinositol levels between the three groups of animals. Pentosidine and other AGEs were increased two- to three-fold in the diabetic animals (p< or =0.001) although treatment with Sulindac did not affect their accumulation in diabetic skin collagen or alter diabetes-induced rises in plasma malondialdehyde. Retinal capillary basement membrane volume was significantly increased in the untreated diabetic dogs compared to non-diabetic controls or Sulindac-treated diabetic animals (p< or =0.0001).


CONCLUSIONS
This study has confirmed the beneficial effect of a non-steroidal anti-inflammatory drug on the early vascular pathology of diabetic retinopathy. However the treatment benefit was not dependent on inhibition of polyol pathway activity, advanced glycation, or oxidative stress.
Gardiner
T A
TA
Department of Ophthalmology, Institute of Clinical Science, Queen's University of Belfast, Royal Victoria Hospital, Northern Ireland, UK.
Anderson
H R
HR
Degenhardt
T
T
Thorpe
S R
SR
Baynes
J W
JW
Archer
D B
DB
Stitt
A W
AW
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000975:Antioxidants / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D003930:Diabetic Retinopathy / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004285:Dogs; D017127:Glycation End Products, Advanced / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D012016:Reference Values; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D012867:Skin / Q000378:metabolism; D013467:Sulindac / Q000627:therapeutic use*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D017127:Glycation End Products, Advanced; D013467:Sulindac; D003094:Collagen