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June 7, 2023 • ✎ STRIA TECH

Systemic Treatment with Pioglitazone Reverses Vision Loss in Preclinical Glaucoma Models

Topics:

Glaucoma

Neuroinflammation

Retinal Degeneration and Inherited Retinal Disease

Retinal Ganglion Cell Pathology

The Optic Nerve, its Neurons and Diseases

Publication

Biomolecules (Feb 09, 2022) Systemic Treatment with Pioglitazone Reverses Vision Loss in Preclinical Glaucoma Models

Zeng H, Dumitrescu AV, Wadkins D, Elwood BW, Gramlich OW, Kuehn MH

DOI: 10.3390/biom12020281 >>

In two mouse models of Glaucoma, Zeng et al show that Pioglitazone, given orally, can reduce or even reverse vision loss. Pioglitazone reduces inflammatory responses. The positive effects could be observed even with continued elevation of intraocular pressure, suggesting that the neuroinflammation experienced during Glaucoma may be more harmful than the elevated pressure.

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 max-imal 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 intraocu-lar pressure to investigate whether oral low-dose pioglitazone treatment preserves retinal ganglion cell (RGC) sur-vival. We then used an inducible glaucoma model in C57BL/6J mice to determine visual function, pattern electro-retinographs, and tracking of optokinetic reflex. Our findings demonstrate that pioglitazone treatment does signifi-cantly protect RGCs and prevents axonal degeneration in the glaucomatous retina. Furthermore, treatment pre-serves 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.