DOES LATANOPROST EXACERBATE RGC LOSS?

 

INTRODUCTION:

Parvin Niknam and colleagues from the Mayo Clinic, USA, have compared diazoxide (DZ), an ATP-sensitive potassium channel opener and latanoprost free acid (LFA), the active metabolite of the prostaglandin analogue latanoprost, on IOP, retinal ganglion cell (RGC) density, retinal morphology, and glial cell activation in the DBA/2J mouse model of pigment dispersion glaucoma.

Therapeutics that open ATP-sensitive potassium (KATP) channels, such as diazoxide (7-chloro−3-methyl-4H−1,2,4-benzothiadiazine 1,1-dioxide; DZ), are an emerging strategy for IOP reduction and direct neuroprotection through multiple mechanisms.

DZ is an FDA approved agent for treating hyperinsulinism and hyperphagia in Prader-Willi Syndrome, and to treat systemic hypertension.

METHODOLOGY:

DBA/2J mice age 4 months received daily topical applications of DZ (5 mM) or LFA (0.1 mM) in one eye, while the fellow eye received the 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:

The study was significant in that it found that IOP was reduced by both DZ (30%) and LFA (24%) for a portion of the experimental period. However, importantly, 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.

CONCLUSION:

The study concluded that DZ lowered IOP without notable retinal side effects. In contrast, LFA reduced IOP but was associated with enhanced RGC neurodegeneration and increased neuroinflammation.

The findings suggest that prostaglandin analog therapy might carry risks of enhanced neurodegeneration in eyes with pre-existing pro-inflammatory microenvironments, though further research is needed outside the DBA/2J strain.

REFERENCE:

Parvin Niknam, Mohammed E. Omer, Kjersten J. Anderson, Tommy A. Rinkoski, Uttio Roy Chowdhury, Gavin W. Roddy. Daily topical latanoprost free acid exacerbates retinal ganglion cell degeneration in the DBA/2J mouse model of pigment dispersion glaucoma. Prostaglandins & Other Lipid Mediators, Volume 186, 2026, 107101, ISSN 1098-8823. https://doi.org/10.1016/j.prostaglandins.2026.107101.