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.
