Abstract
Purpose :
Diabetic cataract can be seen in young diabetic patients even with good glycemic control and it is a significant complication leading to visual acuity loss. We investigated the involvement of oxidative stress overproduction by renin-angiotensin system (RAS) on cataract formation in hyperglycemic rats by the administration of angiotensin II receptor blocker (ARB).
Methods :
Eight-week-old-male Wistar rats made hyperglycemic by streptozotocin (STZ), as well as control rats, received candesartan (2.5mg/kg/day) or normal food orally from 10 weeks until sacrifice (18 weeks). Cataract progression was evaluated by using slit-lamp examination at 8, 12, and 17 weeks. At 18 weeks, the animals were euthanized, and the whole lens was removed. Tissue localization and expression of oxidative stress in their lenses were assessed by immunohistochemistry and RT-PCR.
Results :
In STZ rats, lens opacity occurred on 12 weeks, and cortical cataracts were observed at the time of removal. Cataract progression was inhibited in the ARB-treated group compared to the placebo-treated group. (p<0.05). RT-PCR showed that ACE expression was upregulated in STZ rats compared to the control group. Oxidative stress-related factors such as NOX-1, NOX-4 and iNOS were upregulated in the placebo-treated group and suppressed in the ARB-treated group. There was a positive correlation between ACE level and oxidative stress-related factors, and a negative correlation between ACE and SOD, an antioxidant-related factor. The oxidative stress-related factors and advanced glycation end products were highly localized in the cortex of the lens in the control group.
Conclusions :
Overproduction of angiotensin II with the increased localized ACE in the lens, which promotes oxidative stress through the upregulations of NOX-1, NOX-4 and iNOS, is possibly involved with diabetic cataract. Earlier administration of ARB or ACE blocker might be helpful for the delay of progression in diabetic cataracts.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.