Therapeutic Effects of PPARα Agonists on Diabetic Retinopathy in Type 1 Diabetes Models

Chen, Ying; Hu, Yang; Lin, Mingkai; Jenkins, Alicia J.; Keech, Anthony; Mott, Robert; Lyons, Timothy J.; Xing, Jian

doi:10.2337/db11-0413

Cited by 148 publications

(175 citation statements)

References 43 publications

(49 reference statements)

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“…These PPAR-␣ agonists exhibit improvement of flow-mediated dilation of bronchial arteries in type 2 diabetes mellitus patients (25) and diabetic retinopathy in type I diabetic animal models (47). Thus, we asked whether this drug could be potentially beneficial in SCD treatment, given our experimental observation that miR-199a2 synthesis was positively regulated by PPAR␣.…”

Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator-activated Receptor-α-mediated Transcription of miR-199a2 Attenuates Endothelin-1 Expression via Hypoxia-inducible Factor-1α

Li¹,

Mpollo

Gonsalves³

et al. 2014

Journal of Biological Chemistry

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Background: Elevated plasma levels of PlGF are associated with increased endothelin-1 and pulmonary hypertension (PH) in SCD. Results: miR-199a2, which targets HIF-1␣ mRNA, located in host gene DNM3os is co-transcriptionally regulated by PPAR␣. Conclusion: PPAR␣ agonist induction of miR-199a2 reduced ET-1 levels. Significance: PPAR␣ agonist reduction of ET-1 levels via induced miR-199a2 provides an alternative strategy to ameliorate PH.

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Section: Discussionmentioning

confidence: 99%

Peroxisome Proliferator-activated Receptor-α-mediated Transcription of miR-199a2 Attenuates Endothelin-1 Expression via Hypoxia-inducible Factor-1α

Li¹,

Mpollo

Gonsalves³

et al. 2014

Journal of Biological Chemistry

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“…Adherent leukocytes can themselves damage the retinal vascular endothelium [208]. Leukocyte adherence is a biomarker of diabetic retinopathy and often used as surrogate endpoint in animal model research, as we did in demonstrating the benefit of fenofibrate in reducing retinal inflammation and diabetic retinopathy [209].…”

Section: Inflammationmentioning

confidence: 64%

“…In the hypertensive Ren-2 rat model of diabetic retinopathy, intravitreal FT011 reduced retinal leukostasis, microglial density, and ICAM-1 mRNA levels [229]. Similarly, systemic and ocular fenofibrate reduced retinal inflammation (and angiogenesis) in rodent models of diabetic retinopathy [209].…”

Section: Inflammationmentioning

confidence: 97%

Biomarkers in Diabetic Retinopathy

et al. 2015

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■ AbstractThere is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat diabetic retinopathy, there is need to reliably identify and triage people with diabetes. Biomarkers may facilitate a better understanding of diabetic retinopathy, and contribute to the development of novel treatments and new clinical strategies to prevent vision loss in people with diabetes. This article reviews key aspects related to biomarker research, and focuses on some specific biomarkers relevant to diabetic retinopathy.

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“…These mechanisms have been recently reviewed [57,60] and are summarized in Fig. (4) [61][62][63][64][65][66].…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

Non-Traditional Systemic Treatments for Diabetic Retinopathy: An Evidence-Based Review

Simó

Ballarini²,

Cunha‐Vaz³

et al. 2015

CMC

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Abstract:The rapid escalation in the global prevalence diabetes, with more than 30% being afflicted with diabetic retinopathy (DR), means it is likely that associated vision-threatening conditions will also rise substantially. This means that new therapeutic approaches need to be found that go beyond the current standards of diabetic care, and which are effective in the early stages of the disease. In recent decades several new pharmacological agents have been investigated for their effectiveness in preventing the appearance and progression of DR or in reversing DR; some with limited success while others appear promising. This up-to-date critical review of non-traditional systemic treatments for DR is based on the published evidence in MEDLINE spanning 1980-December 2014. It discusses a number of therapeutic options, paying particular attention to the mechanisms of action and the clinical evidence for the use of renin-angiotensin system blockade, fenofibrate and calcium dobesilate monohydrate in DR.

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Therapeutic Effects of PPARα Agonists on Diabetic Retinopathy in Type 1 Diabetes Models

Cited by 148 publications

References 43 publications

Peroxisome Proliferator-activated Receptor-α-mediated Transcription of miR-199a2 Attenuates Endothelin-1 Expression via Hypoxia-inducible Factor-1α

Peroxisome Proliferator-activated Receptor-α-mediated Transcription of miR-199a2 Attenuates Endothelin-1 Expression via Hypoxia-inducible Factor-1α

Biomarkers in Diabetic Retinopathy

Non-Traditional Systemic Treatments for Diabetic Retinopathy: An Evidence-Based Review

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