Systemic Treatment with Pioglitazone Reverses Vision Loss in Preclinical Glaucoma Models

Huilan Zeng; Alina V Dumitrescu; David Wadkins; Benjamin W Elwood; Oliver W Gramlich; Markus H Kuehn

doi:10.3390/biom12020281

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Systemic Treatment with Pioglitazone Reverses Vision Loss in Preclinical Glaucoma Models

Journal article

Open access

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Systemic Treatment with Pioglitazone Reverses Vision Loss in Preclinical Glaucoma Models

Huilan Zeng, Alina V Dumitrescu, David Wadkins, Benjamin W Elwood, Oliver W Gramlich and Markus H Kuehn

Biomolecules (Basel, Switzerland), Vol.12(2), p.281

02/09/2022

DOI: 10.3390/biom12020281

PMCID: PMC8961625

PMID: 35204782

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Abstract

Neuroinflammation significantly contributes to the pathophysiology of several neurodegenerative diseases. This is also the case in glaucoma and may be a reason why many patients suffer from progressive vision loss despite maximal reduction in intraocular pressure. Pioglitazone is an agonist of the peroxisome proliferator-activated receptor gamma (PPARγ) whose pleiotrophic activities include modulation of cellular energy metabolism and reduction in inflammation. In this study we employed the DBA2/J mouse model of glaucoma with chronically elevated intraocular pressure to investigate whether oral low-dose pioglitazone treatment preserves retinal ganglion cell (RGC) survival. We then used an inducible glaucoma model in C57BL/6J mice to determine visual function, pattern electroretinographs, and tracking of optokinetic reflex. Our findings demonstrate that pioglitazone treatment does significantly protect RGCs and prevents axonal degeneration in the glaucomatous retina. Furthermore, treatment preserves and partially reverses vision loss in spite of continuously elevated intraocular pressure. These data suggest that pioglitazone may provide treatment benefits for those glaucoma patients experiencing continued vision loss.

pioglitazone

glucose metabolism

glaucoma

PPARγ

Details

Title: Subtitle: Systemic Treatment with Pioglitazone Reverses Vision Loss in Preclinical Glaucoma Models
Creators: Huilan Zeng - Human Clinical Research Center of Ophthalmic Disease, Changsha 410011, China
Alina V Dumitrescu - Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, IA 52242, USA
David Wadkins - Iowa City VA Center for the Prevention and Treatment of Visual Loss, Iowa City, IA 52246, USA
Benjamin W Elwood - Iowa City VA Center for the Prevention and Treatment of Visual Loss, Iowa City, IA 52246, USA
Oliver W Gramlich - Iowa City VA Center for the Prevention and Treatment of Visual Loss, Iowa City, IA 52246, USA
Markus H Kuehn - Iowa City VA Center for the Prevention and Treatment of Visual Loss, Iowa City, IA 52246, USA
Resource Type: Journal article
Publication Details: Biomolecules (Basel, Switzerland), Vol.12(2), p.281
DOI: 10.3390/biom12020281
PMID: 35204782
PMCID: PMC8961625
NLM abbreviation: Biomolecules
eISSN: 2218-273X
Grant note: 1I50RX003002-01 / United States Department of Veterans Affairs 1 I01 RX002860 / United States Department of Veterans Affairs
Language: English
Date published: 02/09/2022
Academic Unit: Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Ophthalmology and Visual Sciences
Record Identifier: 9984222805602771

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