Systemic Pentosan Polysulfate Administration Causes Retinal Function Loss in the C57Bl/6J Mouse

Abstract

Purpose : Pentosan Polysulfate Sodium (PPS) is a United States Food and Drug Administration-approved drug for the management of bladder pain or discomfort associated with interstitial cystitis. We recently reported a novel maculopathy suggestive of a primary retinal pigment epithelium (RPE) injury in patients with a history of chronic PPS use [Pearce, Chen, Jain 2018]. In an initial prospective test of effects of systemic PPS administration on visual outcomes, we injected mice intraperitoneally with PPS and measured their ocular function and morphology for several weeks.

Methods : Five male C57Bl/6J mice were given intraperitoneal injections of phosphate buffered saline (PBS) or PPS in PBS or (2 vehicle, 3 drug). Injections were given daily, 6 days a week for 28 days. Concentration of drug was 25 mg/kg mouse weight. Once a week mice underwent non-invasive assays: retinal function was assessed by electroretinography (ERG), retinal morphology was assessed by spectral domain-optical coherence tomography (SD-OCT), and retinal angiography was assessed by confocal scanning laser ophthalmoscopy (cSLO).

Results : Over 17 days in which we gave 15 injections, we saw a main drug effect on ERG a- and b-wave amplitudes (p=0.0362 and 0.0458, respectively, two-way repeated measures ANOVA). At the end of this period, mean ERG a-wave amplitude was 20% lower in the drug-treated animals, and B-wave amplitude was 10% lower. Differences in in-vivo imaging were less pronounced, but, beginning in the third week of the study, one mouse receiving PPS did develop abnormal spots of discoloration on the fundus of one eye.

Conclusions : Systemic administration of PPS causes retinal deficits. The current pilot study tested high doses over a relatively short duration, while our ongoing studies are testing chronic administration effects. We expect that this model will be useful for testing mechanistic hypotheses and could lead to unexpected discoveries in retinal biology.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.