Re: Shin et al.: Patterns of progressive ganglion cell–inner plexiform layer thinning in glaucoma detected by OCT (Ophthalmology. 2018;125:1515-1525)

Abstract

This task may prove to be difficult. PPS, which has a molecular structure similar to glycosaminoglycans, is thought to have numerous biological activities. In vitro studies have demonstrated anti-inflammatory, fibrinolytic, and anticoagulant properties among others, with myriad of putative molecular mechanisms. Indeed, the mechanism of action of PPS in interstitial cystitis itself is not wellunderstood. Interestingly, this drug is a proposed therapy for many unrelated diseases. A common theme is that these diseases, including osteoarthritis, CreutzfeldteJakob disease, mucopolysaccharidoses, psychotic disorders, and interstitial cystitis, are notoriously difficult to manage and have limited alternative therapies available.Greenlee et al have identified chronic antagonism of fibroblast growth factor (FGF) signaling as a possible culprit in PPSassociated maculopathy. They note the varied roles FGF signaling plays within the retina, and in particular the importance of FGFdirected injury responses. This line of inquiry will be important. FGF signaling, which involves dozens of FGF subtypes and FGF receptors, serves many roles throughout the body. It is worth exploring whether PPS has other off-target effects outside of the eye related to chronic inhibition of FGF signaling. Further, as suggested by the authors, it will be useful to explore the impact of other FGF antagonists on the health of the retina and the retinal pigment epithelium.Our clinical observations suggest that the primary cellular insult in PPS-associated maculopathy is within the retinal pigment epithelium. We are particularly interested in the resemblance of this condition to various macular dystrophies, which suggests a disruption in normal photoreceptoreretinal pigment epithelium homeostasis. These mechanisms are the subject of our ongoing investigations in the laboratory. This work may in turn lead to greater understanding of diseases such as age-related macular degeneration and macular dystrophies.We hope that our initial observation and thoughtful comments such as those by Greenlee et al will lead to greater understanding of the impact of PPS on the macula, and may ultimately elucidate unanticipated insights into retinal biology. cussion of the limitations of the present study but seek clarification of the points we have raised.