NDLI: FT011, a Novel Cardiorenal Protective Drug, Reduces Inflammation, Gliosis and Vascular Injury in Rats with Diabetic Retinopathy

Content Provider	PubMed Central
Author	Devy, Deliyanti Zhang, Yuan Khong, Fay Berka, David R. Stapleton, David I. Kelly, Darren J. Wilkinson-berka, Jennifer L.
Editor	Boulton, Michael E.
Copyright Year	2015
Abstract	Diabetic retinopathy features inflammation as well as injury to glial cells and the microvasculature, which are influenced by hypertension and overactivity of the renin-angiotensin system. FT011 is an anti-inflammatory and anti-fibrotic agent that has been reported to attenuate organ damage in diabetic rats with cardiomyopathy and nephropathy. However, the potential therapeutic utility of FT011 for diabetic retinopathy has not been evaluated. We hypothesized that FT011 would attenuate retinopathy in diabetic Ren-2 rats, which exhibit hypertension due to an overactive extra-renal renin-angiotensin system. Diabetic rats were studied for 8 and 32 weeks and received intravitreal injections of FT011 (50 μM) or vehicle (0.9% NaCl). Comparisons were to age-matched controls. In the 8-week study, retinal inflammation was examined by quantitating vascular leukocyte adherence, microglial/macrophage density and the expression of inflammatory mediators. Macroglial Müller cells, which exhibit a pro-inflammatory and pro-angiogenic phenotype in diabetes, were evaluated in the 8-week study as well as in culture following exposure to hyperglycaemia and FT011 (10, 30, 100 μM) for 72 hours. In the 32-week study, severe retinal vasculopathy was examined by quantitating acellular capillaries and extracellular matrix proteins. In diabetic rats, FT011 reduced retinal leukostasis, microglial density and mRNA levels of intercellular adhesion molecule-1 (ICAM-1). In Müller cells, FT011 reduced diabetes-induced gliosis and vascular endothelial growth factor (VEGF) immunolabeling and the hyperglycaemic-induced increase in ICAM-1, monocyte chemoattractant protein-1, CCL20, cytokine-induced neutrophil chemoattractant-1, VEGF and IL-6. Late intervention with FT011 reduced acellular capillaries and the elevated mRNA levels of collagen IV and fibronectin in diabetic rats. In conclusion, the protective effects of FT011 in cardiorenal disease extend to key elements of diabetic retinopathy and highlight its potential as a treatment approach.
Related Links	http://dx.doi.org/10.1371/journal.pone.0134392
Starting Page	134392
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	7
Volume Number	10
Language	English
Publisher	Public Library of Science
Publisher Date	2015-07-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Short Pulse Duration High-Power Laser Photocoagulation during Vitrectomy for Diabetic Retinopathy Reduces Postoperative Inflammation

Novel Diabetic Mouse Models as Tools for Investigating Diabetic Retinopathy

Ginkgolide B Reduces Atherogenesis and Vascular Inflammation in ApoE−/− Mice

Retinitis Pigmentosa Reduces the Risk of Proliferative Diabetic Retinopathy: A Nationwide Population-Based Cohort Study

The Effect of Lithospermic Acid, an Antioxidant, on Development of Diabetic Retinopathy in Spontaneously Obese Diabetic Rats

High Prevalence of Diabetic Retinopathy in Diabetic Patients Concomitant with Metabolic Syndrome

Mebendazole Reduces Vascular Smooth Muscle Cell Proliferation and Neointimal Formation Following Vascular Injury in Mice

Baicalein Reduces Airway Injury in Allergen and IL-13 Induced Airway Inflammation

Pyruvate Administration Reduces Recurrent/Moderate Hypoglycemia-Induced Cortical Neuron Death in Diabetic Rats

FT011, a Novel Cardiorenal Protective Drug, Reduces Inflammation, Gliosis and Vascular Injury in Rats with Diabetic Retinopathy

Similar Documents

Short Pulse Duration High-Power Laser Photocoagulation during Vitrectomy for Diabetic Retinopathy Reduces Postoperative Inflammation

Novel Diabetic Mouse Models as Tools for Investigating Diabetic Retinopathy

Ginkgolide B Reduces Atherogenesis and Vascular Inflammation in ApoE−/− Mice

Retinitis Pigmentosa Reduces the Risk of Proliferative Diabetic Retinopathy: A Nationwide Population-Based Cohort Study

The Effect of Lithospermic Acid, an Antioxidant, on Development of Diabetic Retinopathy in Spontaneously Obese Diabetic Rats

High Prevalence of Diabetic Retinopathy in Diabetic Patients Concomitant with Metabolic Syndrome

Mebendazole Reduces Vascular Smooth Muscle Cell Proliferation and Neointimal Formation Following Vascular Injury in Mice

Baicalein Reduces Airway Injury in Allergen and IL-13 Induced Airway Inflammation

Pyruvate Administration Reduces Recurrent/Moderate Hypoglycemia-Induced Cortical Neuron Death in Diabetic Rats

FT011, a Novel Cardiorenal Protective Drug, Reduces Inflammation, Gliosis and Vascular Injury in Rats with Diabetic Retinopathy