Systemic Treatment with Pioglitazone Reverses Vision Loss in Preclinical Glaucoma Models

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 p...

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Bibliographic Details
Published in:Biomolecules (Basel, Switzerland) Switzerland), 2022-02, Vol.12 (2), p.281
Main Authors: Zeng, Huilan, Dumitrescu, Alina V, Wadkins, David, Elwood, Benjamin W, Gramlich, Oliver W, Kuehn, Markus H
Format: Article
Language:English
Subjects:
Alzheimer's disease
Animal models
Animals
Cell survival
Energy metabolism
Glaucoma
Glaucoma - metabolism
glucose metabolism
Humans
Inflammation
Intraocular Pressure
Laboratories
Medical research
Mice
Mice, Inbred C57BL
Neurodegeneration
Neurodegenerative diseases
Optic nerve
Optokinetic response
Patients
Peroxisome proliferator-activated receptors
Pioglitazone
Pioglitazone - pharmacology
Pioglitazone - therapeutic use
PPARγ
Pressure
Retina
Retinal ganglion cells
Retinal Ganglion Cells - metabolism
Vision
Visual perception
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Summary: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.
ISSN:2218-273X
2218-273X
DOI:10.3390/biom12020281