title: Biochemical and ultrastructural studies in the neural retina and retinal pigment epithelium of STZ-diabetic rats: effect of captopril.
abstract: We measured the activities of total Na+, K+-ATPase (Na, K-ATPase), its alpha1 and alpha2/alpha3 isoforms and the angiotensin-converting enzyme (ACE) in the microvascular and neural compartments of the retina, and/or retinal pigment epithelium (RPE) of streptozotocin (STZ)-diabetic rats. The effect of captopril, an ACE inhibitor on Na, K-ATPase activities was also determined and correlated to morphological changes. Insulin-dependent diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg) in male Long-Evans rats. ACE activity was inhibited by captopril (10 mg/kg given in the drinking water) for 1 month. Na, K-ATPase activity was measured spectrophotometrically or by a radioassay (32P-labeled ATP). The activity of ACE was determined by a radioassay using tritiated benzoyl-gly-gly-gly as substrate. Both the alpha1 and alpha2/alpha3 isoforms of Na, K-ATPase were present in the microvascular and neural compartments of retinas, whereas only one isoform, the alpha2/alpha3, was found in the RPE. In 2-month diabetic rats, the activity of the alpha2/alpha3 isoform was reduced in both the microvascular and neural compartments of retinas, while the activity of the alpha1 isoform was reduced only in the neural isolates. ACE activity was significantly decreased in the retinal neural compartment and unaltered in the microvascular compartment from 2-month diabetic rats. In 5-month diabetic rats, Na, K-ATPase activity was moderately but not significantly reduced in RPE preparations. Ultrastructural studies revealed a significant deepening of basal infoldings in the RPE and a noticeable increase in the size of the extracellular space between the basal infoldings of 5-month diabetic animals. Captopril stimulated Na, K-ATPase activity in the neural retina, but not in the RPE. Diabetes-induced morphological changes in the RPE were not improved by captopril. An enlargement of intercellular space between the RPE cells was a frequent finding in the treated group. In conclusion, captopril stimulated Na, K-ATPase activity in the neural retina of diabetic rats. This stimulation seems to be beneficial to the neural retina. ACE inhibition, however, did not improve RPE morphological changes. Although the clinical significance of increased intercellular spacing between RPE cells in treated animals is not clearly established, we speculate that it might contribute to an increased alteration of their barrier function. Additional studies are necessary to assess both the desirable and adverse effects of captopril and other ACE inhibitors in the retinas of diabetic patients.
authors.affiliation: College of Optometry, University of Houston, Texas, USA.
authors.forename: T
authors.initials: T
authors.lastname: Bensaoula
authors.forename: A
authors.initials: A
authors.lastname: Ottlecz
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002216:Captopril / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D003930:Diabetic Retinopathy / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D000254:Sodium-Potassium-Exchanging ATPase