Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression

Kapil Chaudhary, Wanwisa Promsote, Sudha Ananth, Rajalakshmi Veeranan-Karmegam, Amany Mohamed Tawfik, Pachiappan Arjunan, Pamela Moore Martin, Sylvia B Smith, Muthusamy Thangaraju, Oleg Kisselev, Vadivel Ganapathy, Jaya Pranava Gnana-Prakasam

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Abstract

Diabetic retinopathy (DR) is a leading cause of blindness among working-age adults. Increased iron accumulation is associated with several degenerative diseases. However, there are no reports on the status of retinal iron or its implications in the pathogenesis of DR. In the present study, we found that retinas of type-1 and type-2 mouse models of diabetes have increased iron accumulation compared to non-diabetic retinas. We found similar iron accumulation in postmortem retinal samples from human diabetic patients. Further, we induced diabetes in HFE knockout (KO) mice model of genetic iron overload to understand the role of iron in the pathogenesis of DR. We found increased neuronal cell death, vascular alterations and loss of retinal barrier integrity in diabetic HFE KO mice compared to diabetic wildtype mice. Diabetic HFE KO mouse retinas also exhibited increased expression of inflammation and oxidative stress markers. Severity in the pathogenesis of DR in HFE KO mice was accompanied by increase in retinal renin expression mediated by G-protein-coupled succinate receptor GPR91. In light of previous reports implicating retinal renin-angiotensin system in DR pathogenesis, our results reveal a novel relationship between diabetes, iron and renin-angiotensin system, thereby unraveling new therapeutic targets for the treatment of DR.

Original languageEnglish (US)
Article number3025
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Iron Overload
Diabetic Retinopathy
Renin
Iron
Knockout Mice
Retina
Renin-Angiotensin System
Genetic Models
Succinic Acid
Blindness
G-Protein-Coupled Receptors
Blood Vessels
Oxidative Stress
Cell Death
Inflammation
Therapeutics

ASJC Scopus subject areas

  • General

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Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression. / Chaudhary, Kapil; Promsote, Wanwisa; Ananth, Sudha; Veeranan-Karmegam, Rajalakshmi; Tawfik, Amany Mohamed; Arjunan, Pachiappan; Martin, Pamela Moore; Smith, Sylvia B; Thangaraju, Muthusamy; Kisselev, Oleg; Ganapathy, Vadivel; Gnana-Prakasam, Jaya Pranava.

In: Scientific Reports, Vol. 8, No. 1, 3025, 01.12.2018.

Research output: Contribution to journalArticle

Chaudhary, Kapil ; Promsote, Wanwisa ; Ananth, Sudha ; Veeranan-Karmegam, Rajalakshmi ; Tawfik, Amany Mohamed ; Arjunan, Pachiappan ; Martin, Pamela Moore ; Smith, Sylvia B ; Thangaraju, Muthusamy ; Kisselev, Oleg ; Ganapathy, Vadivel ; Gnana-Prakasam, Jaya Pranava. / Iron Overload Accelerates the Progression of Diabetic Retinopathy in Association with Increased Retinal Renin Expression. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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