Daily Topical Latanoprost Free Acid Exacerbates Retinal Ganglion Cell Degeneration in the DBA/2J Mouse Model of Pigment Dispersion Glaucoma.

PURPOSE: To compare diazoxide (DZ), an ATP-sensitive potassium channel opener and latanoprost free acid (LFA), the active metabolite of the prostaglandin analogue latanoprost, a first-line agent for intraocular pressure (IOP) reduction in patients with glaucoma, on IOP, retinal ganglion cell (RGC) density, retinal morphology, and glial cell activation in the DBA/2J mouse model of pigment dispersion glaucoma. METHODS: DBA/2J mice age 4 months received daily topical applications of DZ (5mM) or LFA (0.1mM) in one eye, while the fellow eye received vehicle. IOP was measured prior to treatment and twice weekly throughout the 23-week treatment period. Immunofluorescence staining was used to quantify RGC density with RNA binding protein with multiple splicing (RBPMS) and glial cell activation as a measure of neuroinflammation with glial fibrillary acidic protein (GFAP). Hematoxylin and eosin staining was used to evaluate retinal morphology. RESULTS: IOP was reduced by both DZ (30%) and LFA (24%) for a portion of the experimental period. DZ did not alter RGC survival, reactive gliosis, or RGC morphology. Conversely, LFA treatment was associated with a significant reduction in RGCs, an increase in reactive gliosis, and altered RGC morphology characteristic of cell death. CONCLUSIONS: DZ lowered IOP without notable retinal side effects. In contrast, LFA reduced IOP but was associated with enhanced RGC neurodegeneration and increased neuroinflammation. Further studies are needed to determine whether LFA-mediated changes are specific to the DBA/2J mouse or if other models with underlying pro-inflammatory microenvironments may be susceptible to RGC loss with prostaglandin analog therapy.