Related Experiment Video
Updated: Sep 27, 2026
An Ex Vivo Choroid Sprouting Assay of Ocular Microvascular Angiogenesis
Published on: August 6, 2020
The renin-angiotensin system influences ocular endothelial cell proliferation in diabetes: transgenic and
Christina J Moravski1, Sandford L Skinner, Anthony J Stubbs
1Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Abstract:
Neovascularization in the retina and iris of diabetic patients is a major cause of severe visual loss. However, study of these lesions is compromised by the lack of a comparable diabetic rodent model. Because the vasoactive and angiogenic agent, angiotensin II, is involved in diabetic microvascular disease, we aimed to determine whether endothelial cell proliferation could be induced in the retinae and irides of hypertensive transgenic (mRen-2)27 rats that display an enhanced extra-renal renin-angiotensin system (RAS), including the eye. Six-week-old Ren-2, spontaneously hypertensive, and Sprague-Dawley rats received either streptozotocin or control vehicle and were studied for 36 weeks. Additional nondiabetic and diabetic Ren-2 rats were treated throughout with the angiotensin-converting enzyme inhibitor lisinopril (LIS) (10 mg/kg/day in drinking water). Endothelial cell proliferation was only observed in retinae and irides of diabetic Ren-2 rats and was reduced with LIS. In diabetic Ren-2, vascular endothelial growth factor (VEGF) and VEGFR-2 mRNA were increased in retinae and irides and reduced with LIS. Diabetes activated ocular renin in Ren-2 but not Sprague-Dawley rats. The diabetic Ren-2 rat is a model of intraocular endothelial cell proliferation that can be attenuated by RAS blockade via VEGF-dependent pathways. RAS blockade is a potential treatment for vision-threatening diabetic microvascular complications.
Insights
Diabetic rats with an activated renin-angiotensin system (RAS) developed eye blood vessel growth. Blocking the RAS with lisinopril reduced this proliferation, suggesting a new treatment for diabetic eye disease.
Area of Science:
- Ophthalmology
- Endocrinology
- Cardiovascular Research
Background:
- Diabetic retinopathy and iris neovascularization cause significant vision loss.
- A suitable rodent model is needed to study these diabetic ocular complications.
- The renin-angiotensin system (RAS) plays a role in diabetic microvascular disease.
Purpose of the Study:
- To investigate endothelial cell proliferation in the retina and iris of diabetic (mRen-2)27 rats with an enhanced RAS.
- To evaluate the effect of angiotensin-converting enzyme (ACE) inhibition on diabetic ocular neovascularization.
Main Methods:
- Diabetic and non-diabetic (mRen-2)27, spontaneously hypertensive, and Sprague-Dawley rats were induced with streptozotocin or vehicle.
- Rats were treated with or without lisinopril (an ACE inhibitor) for 36 weeks.
- Ocular endothelial cell proliferation, VEGF, VEGFR-2 mRNA, and ocular renin activity were assessed.
Main Results:
- Endothelial cell proliferation was observed exclusively in the retinae and irides of diabetic (mRen-2)27 rats.
- Lisinopril treatment significantly reduced ocular endothelial cell proliferation in diabetic (mRen-2)27 rats.
- Vascular endothelial growth factor (VEGF) and VEGFR-2 mRNA levels increased in diabetic (mRen-2)27 rat eyes and decreased with lisinopril treatment.
- Diabetes activated ocular renin in (mRen-2)27 rats but not Sprague-Dawley rats.
Conclusions:
- The diabetic (mRen-2)27 rat serves as a valuable model for studying intraocular endothelial cell proliferation.
- Renin-angiotensin system (RAS) blockade effectively attenuates diabetic ocular neovascularization through VEGF-dependent pathways.
- RAS blockade represents a potential therapeutic strategy for preventing vision-threatening diabetic microvascular complications.
