Pentosan Polysulfate
A semi-synthetic polysulfated xylan (glycosaminoglycan) derived from beechwood. FDA-approved orally (Elmiron) for interstitial cystitis, with widespread off-label use as an injectable for joint and cartilage repair in osteoarthritis. One of the most popular peptide-adjacent therapies in sports medicine and regenerative clinics. Mimics heparan sulfate proteoglycans to protect cartilage and reduce joint inflammation.
Typical Dosage
Oral (Elmiron): 100 mg three times daily for interstitial cystitis. Injectable (compounding): 2-3 mg/kg subcutaneous or intramuscular once or twice weekly for 4-8 weeks for joint applications.
Administration
Oral capsule or subcutaneous/intramuscular injection
Mechanism of Action
Pentosan Polysulfate (PPS) is a semi-synthetic, sulfated polysaccharide derived from beechwood hemicellulose (xylan). Its structure consists of a xylose backbone with sulfate ester groups at positions 2 and 3, giving it a high negative charge density similar to heparin and endogenous glycosaminoglycans like heparan sulfate. This polyanionic character is central to its multiple mechanisms of action.
In joint and cartilage repair, PPS stimulates chondrocyte proteoglycan synthesis — the production of aggrecan and other proteoglycans that form the hydrated gel matrix of articular cartilage. Proteoglycans are responsible for cartilage's compressive resilience and water retention, and their loss is a hallmark of osteoarthritis. PPS also inhibits matrix metalloproteinases (MMPs), particularly MMP-3, MMP-9, and MMP-13, which are the enzymes responsible for cartilage matrix degradation in osteoarthritis. By simultaneously promoting matrix synthesis and inhibiting matrix breakdown, PPS shifts the balance toward cartilage repair. Additionally, PPS improves synovial fluid viscosity by stimulating hyaluronic acid synthesis from synoviocytes, partially restoring the lubrication and shock-absorbing properties lost in arthritic joints.
PPS has several additional pharmacological properties. It inhibits complement activation (particularly the alternative pathway), reducing inflammatory damage to joint tissues. It has fibrinolytic activity — promoting the dissolution of fibrin deposits that can form in inflamed synovial tissue and contribute to joint adhesions. It inhibits certain lipases and has lipid-clearing properties. In its FDA-approved indication (interstitial cystitis), PPS is thought to replenish the damaged glycosaminoglycan layer lining the bladder epithelium, restoring the protective barrier against urine irritants. The recent FDA warning about retinal pigmentary maculopathy with long-term oral use (affecting approximately 1 in 4 long-term users) appears to be related to accumulation of PPS metabolites in the retinal pigment epithelium, where they may disrupt lysosomal function and pigment recycling.
Regulatory Status
FDA approved as Elmiron (oral) for interstitial cystitis. Injectable form used widely in veterinary medicine and available through compounding pharmacies for human use.
Risks & Safety
Common: bruising, injection site pain, headache, nausea, diarrhea, alopecia (oral). Serious: retinal pigmentary maculopathy with long-term oral use (FDA warning — unique, potentially irreversible vision damage), hepatotoxicity (rare). Rare: thrombocytopenia, severe allergic reactions. Regular ophthalmologic exams recommended with oral use beyond 2 years. FDA approved for interstitial cystitis (Elmiron).
Research Papers
2Published: September 16, 2026
Abstract
We evaluated the value of baseline structural optical coherence tomography (OCT) biomarkers in determining functional treatment response at 6,12-, and 24-months following treatment initiation in patients undergoing anti-vascular endothelial growth factor, steroid, or laser treatment for diabetic macular edema (DME). Ovid MEDLINE, EMBASE, and Web of Science databases were searched from inception for studies evaluating the association between baseline OCT biomarkers and best-recorded central visual acuity (VA). A synthesis using vote counting based on the direction of effect in relation to a five-letter minimally important difference was used. GRADE guidelines informed the certainty of evidence. Ninety-six studies evaluating 29 biomarkers were included. No biomarker with at least 'Low' certainty was associated with improved VA. Greater baseline ellipsoid zone (EZ) disruption and hyperreflective foci were associated with decreased VA at 6 months with "Low" certainty of evidence. There was also "Low" certainty that increased baseline disorganization of the retinal inner layers, increased baseline disruption of the external limiting membrane or EZ were associated with decreased VA at 12 months. No biomarker was associated with a poor prognosis with at least 'Moderate' certainty. The certainty was downgraded due to inadequately controlling for confounders and a lack of standardization regarding how biomarkers were defined and outcomes were measured.
Published: September 3, 2026
Abstract
This systematic review examines the prognostic value of baseline optical coherence tomography (OCT) biomarkers in predicting visual acuity (VA) outcomes for eyes with macular edema secondary to retinal vein occlusions (RVO) treated with anti-VEGF therapies, steroids, laser photocoagulation, or combination treatments. VA predictions at 6, 12, and 24 months post-treatment were assessed using a narrative synthesis approach and vote counting based on effect direction relative to a minimal clinically important difference. Certainty of evidence was evaluated using GRADE guidelines. Confounding factors, biomarker variability, and inconsistent outcome measurements were critically analyzed. A total of 116 studies assessing 31 unique OCT biomarkers were included. 'Low' certainty evidence indicated that an intact external limiting membrane (ELM) at baseline predicted better VA at 6 months, while baseline ellipsoid zone (EZ) integrity predicted better VA at 12 months at 5-letter change, however, these associations were not observed at thresholds of 10 and 15 letters. Certainty of evidence was often downgraded due to confounding factors, variability in biomarker definitions, and inconsistent outcomes. These findings highlight OCT biomarkers' potential for prognostication in RVO patients, but underscore the need for standardized definitions and further research to address confounders, improving the reliability and clinical utility of OCT-based biomarkers.
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