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Pentosan Polysulfate Sodium Causes Diminished Function and Subtle Morphological Changes in Retina and RPE of Mice

Investigative Ophthalmology & Visual Science · 11 authors, 6 centres

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TL;DR

This preclinical mouse study administered pentosan polysulfate sodium (PPS) via diet for 14 months and found that it caused a decline in retinal and retinal pigment epithelium (RPE) function, measured by electroretinography, alongside subtle morphological changes in RPE cells.

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Retinal and RPE function was assessed by electroretinography (ERG) at regular intervals. After 10 months, a significant diminution in mean scotopic c-wave amplitudes was observed. By 11 months, diminutions in mean scotopic a- and b-wave amplitudes were also seen. Post-mortem analysis of RPE flatmounts revealed altered cell morphology, including increased mean en face cell area and geometric eccentricity, decreased cell solidity and extent, and cytosolic translocation of alpha-catenin. Shortened photoreceptor outer segments were also noted. The authors conclude that PPS treatment causes slowly progressing RPE and photoreceptor damage in mice, potentially offering a model for studying retinal pathologies.

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other

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ophthalmology

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ORIGINAL PAPER

PMC10893900

Pentosan Polysulfate Sodium Causes Diminished Function and Subtle Morphological Changes in Retina and RPE of Mice

Investigative Ophthalmology & Visual Science

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ABSTRACT

Purpose There are numerous reports of a distinctive maculopathy in adults exposed to pentosan polysulfate sodium (PPS), a drug prescribed to treat bladder discomfort associated with interstitial cystitis. We tested whether PPS treatment of mice injures RPE or retina to provide insight into the etiology of the human condition. Methods Mice were fed PPS-supplemented chow over 14 months. RPE and retinal function was assessed by electroretinography (ERG) regularly. Following euthanasia, one eye was used for sagittal sectioning and histology, the contralateral for RPE flatmounting. ZO-1 positive RPE cell borders were imaged using confocal microscopy and cell morphology was analyzed using CellProfiler. Results After 10 months of PPS treatment, we observed diminution of mean scotopic c-wave amplitudes. By 11 months, we additionally observed diminutions of mean scotopic a- and b-wave amplitudes. Analysis of flatmounts revealed altered RPE cell morphology and morphometrics in PPS-treated mice, including increased mean en face cell area and geometric eccentricity, decreased RPE cell solidity and extent, and cytosolic translocation of alpha-catenin, all markers of RPE cell stress. Sex and regional differences were seen in RPE flatmount measures. Shortened photoreceptor outer segments were also observed. Conclusions PPS treatment reduced RPE and later retina function as measured by ERG, consistent with a primary RPE injury. Post-mortem analysis revealed extensive RPE pleomorphism and polymegathism and modest photoreceptor changes. We conclude that PPS treatment of mice causes slowly progressing RPE and photoreceptor damage and thus may provide a useful model for some retinal pathologies.

CITATION EXPORT

Preston E. Girardot, Xian Zhang, Nan Zhang et al.. Pentosan Polysulfate Sodium Causes Diminished Function and Subtle Morphological Changes in Retina and RPE of Mice. Investigative Ophthalmology & Visual Science. (2024). https://doi.org/10.1167/iovs.65.2.28

AUTHORS

11 · 6 CENTRES

Preston E. Girardot, Xian Zhang, Nan Zhang, Kevin J. Donaldson, Micah A. Chrenek, Jana T. Sellers, Andrew J. Feola, Jack Papania, John M. Nickerson, Nieraj Jain, Jeffrey H. Boatright

1Department of Ophthalmology, Emory University, Atlanta, GA, United States
2Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, United States
3Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, China
4Department of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan, China
5Neuroscience Institute, Georgia State University, Atlanta, GA, United States
6Department of Biomedical Engineering, Georgia Institute of Technology/Emory University, Atlanta, GA, United States