Benefits of Renin-Angiotensin Blockade on Retinopathy in Type 1 Diabetes Vary With Glycemic Control

Harindhanavudhi, Tasma; Mauer, Michael; Klein, Michael L.; Zinman, Bernard; Sinaiko, Alan R.; Caramori, M. L.

doi:10.2337/dc11-0476

Cited by 31 publications

(18 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…DR is one of the most common microvascular complication of diabetes mellitus 111 . Many factors are involved in the pathogenesis of DR such as metabolic disorders like hyperglycemia, high blood pressure, hyperlipidemia, age, and oxidative stress 59, 112.…”

Section: Resultsmentioning

confidence: 99%

Therapeutic targets of renin-angiotensin system in ocular disorders

Choudhary

Kapoor

Singh

et al. 2017

Journal of Current Ophthalmology

138

134

View full text Add to dashboard Cite

PurposeTo review current literature on the renin-angiotensin system (RAS)-mediated pathogenic mechanisms and therapeutic targets in ocular diseases.MethodsA comprehensive literature survey was performed on PubMed, Scopus, and Google Scholar databases published from 1977 to 2016. The search terms were a RAS, angiotensin, angiotensin receptor, prorenin, pro (renin) receptor, angiotensin converting enzyme inhibitor, angiotensin receptor blocker associated with ocular disorders like cataract, glaucoma, diabetic retinopathy (DR), macular degeneration, and uveitis. Articles were reviewed on the basis of the association between ocular disorders and RAS and relevant articles were discussed.ResultsThe literature revealed that the individual RAS components including renin, angiotensins, angiotensin converting enzymes, and RAS receptors have been expressed in the specific ocular tissues like retina, choroid, and ciliary body. The activation of both circulatory and local RAS potentiate the various inflammatory and angiogenic signaling molecules, including vascular endothelial growth factor (VEGF), extracellular signal-regulated kinase, and advanced glycation end products (AGE) in the ocular tissues and leads to several blinding disorders like DR, glaucoma, and macular degeneration. The classical and newer RAS inhibitors have illustrated protective effects on blinding disorders, including DR, glaucoma, macular degeneration, uveitis, and cataract.ConclusionsThe RAS components are present in the extrarenal tissues including ocular tissue and have an imperative role in the ocular pathophysiology. The clinical studies are needed to show the role of therapeutic modalities targeting RAS in the treatment of different ocular disorders.

show abstract

Section: Resultsmentioning

confidence: 99%

Therapeutic targets of renin-angiotensin system in ocular disorders

Choudhary

Kapoor

Singh

et al. 2017

Journal of Current Ophthalmology

138

134

View full text Add to dashboard Cite

show abstract

“…Up-or downregulation of RA system activity does not have to result from alterations in mRNA levels only; the level of protein and activity in the RA system should also be examined. However, inhibitors of the RA system are effective against diabetic retinopathy (13)(14)(15)(16)(17). RA system inhibitors can act through inhibition of ligand production or inhibition of receptor action.…”

Section: Discussionmentioning

confidence: 99%

Effects of Diets with Different Proportions of Protein/ Carbohydrate on Retinal Manifestations in db Mice

Emi

Okatani

Araki

et al. 2018

View full text Add to dashboard Cite

Abstract. Background Diabetic retinopathy is one of the three major complications of diabetes, and it is the leading cause of visual impairment and blindness among adults (1). A recent epidemiological study found diabetic retinopathy prevalence to be 34.6% for individuals with diabetes (2). In the Wisconsin Epidemiological Study of Diabetic Retinopathy, microalbuminuria, representing nephropathy, was associated with the presence of retinopathy in individuals with diabetes (3). The recent rise in the numbers of diabetes and diabetic retinopathy cases worldwide is likely to be related to lifestyle/life environment rather than genetic factors, as a global genetic diversity has not changed appreciably over this short period of time (4-7). Lifestyle factors, including nutrition, have been altered markedly in recent decades (8, 9). Diabetic nephropathy is aggravated by higher intake of total protein (10, 11). However, the impact of altered nutrition, especially protein content, on the development of diabetic retinopathy is not fully understood (10,11,12).Glycemic control and blood pressure control reduce the progression of diabetic retinopathy, and ophthalmological treatment including laser applications plays a prominent role in the control of diabetic retinopathy. However, currently there are no drugs that inhibit the onset or progression of diabetic retinopathy, except for inhibitors of the renin-angiotensin (RA) system (13-17). Regarding nutritional intervention, patients with diabetic retinopathy have been managed by a low-energy diet of suppressed carbohydrate intake and relatively highprotein intake, but the influence of diet on the pathophysiology of retinopathy is not fully understood. A rodent study of diabetic nephropathy reported an additive effect of RA system inhibitors and a low-protein diet on kidney manifestations (18). A low-protein diet may have additional beneficial effects through suppressed expression of genes involved in the kidney RA system. The effect of dietary protein content diets (12-24% energy), which is the range in regular human diets (4, 8), on glucose levels and renal manifestations in db mice (19,20), an animal model for diabetes with leptin-receptor deficiency. In the experiments using db mice, a high-protein, low-carbohydrate diet increased blood glucose levels and exacerbated renal manifestations, compared with a low-protein, high-carbohydrate diet (21,22). The dietary protein content should be examined for its 265

show abstract

“…The Diabetic Retinopathy Candesartan Trials (DIRECT) [14,15], using the ARB candesartan in type 1 and 2 diabetes, showed a clear trend towards less severe retinopathy with RAS blockade. A smaller trial, the Renin-Angiotensin System Study (RASS), reported that RAS blockade with both the ARB losartan and the angiotensin-converting enzyme (ACE) inhibitor, enalapril, resulted in reduced retinopathy progression in type 1 diabetes [16]. Experimental evidence concerning the effect of ARBs is sparse.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of the reninangiotensin system (RAS), mainly by its major effector peptide angiotensin-II and its receptor, angiotensin-II receptor 1 (AT1), has been shown to play an important role in the pathophysiology of diabetic nephropathy, neuropathy and retinopathy [12,13]. Evidence comes mainly from clinical intervention studies [14][15][16]; RAS inhibition partly and selectively ameliorated diabetes-induced changes [16] or reduced the incidence of diabetic retinopathy in patients [15]. The underlying mechanisms, however, have not been systematically explored.…”

Section: Introductionmentioning

confidence: 99%

The TetO rat as a new translational model for type 2 diabetic retinopathy by inducible insulin receptor knockdown

et al. 2016

View full text Add to dashboard Cite

Aims/hypothesis Although the renin-angiotensin system plays an important role in the progression of diabetic retinopathy, its influence therein has not been systematically evaluated. Here we test the suitability of a new translational model of diabetic retinopathy, the TetO rat, for addressing the role of angiotensin-II receptor 1 (AT1) blockade in experimental diabetic retinopathy. Methods Diabetes was induced by tetracycline-inducible small hairpin RNA (shRNA) knockdown of the insulin receptor in rats, generating TetO rats. Systemic treatment consisted of an AT1 blocker (ARB) at the onset of diabetes, following which, 4-5 weeks later the retina was analysed in vivo and ex vivo. Retinal function was assessed by Ganzfeld electroretinography (ERG). Results Retinal vessels in TetO rats showed differences in vessel calibre, together with gliosis. The total number and the proportion of activated mononuclear phagocytes was increased. TetO rats presented with loss of retinal ganglion cells (RGC) and ERG indicated photoreceptor malfunction. Both the inner and outer blood-retina barriers were affected. The ARB treated group showed reduced gliosis and an overall amelioration of retinal function, alongside RGC recovery, whilst no statistically significant differences in vascular and inflammatory features were detected. Conclusions/interpretation The TetO rat represents a promising translational model for the early neurovascular changes associated with type 2 diabetic retinopathy. ARB treatment had an effect on the neuronal component of the retina but not on the vasculature.

show abstract

Benefits of Renin-Angiotensin Blockade on Retinopathy in Type 1 Diabetes Vary With Glycemic Control

Cited by 31 publications

References 23 publications

Therapeutic targets of renin-angiotensin system in ocular disorders

Therapeutic targets of renin-angiotensin system in ocular disorders

Effects of Diets with Different Proportions of Protein/ Carbohydrate on Retinal Manifestations in db Mice

The TetO rat as a new translational model for type 2 diabetic retinopathy by inducible insulin receptor knockdown

Contact Info

Product

Resources

About