Diuretic inhibition of experimental myopia implicates retinal ion-driven efflux in the regulation of ocular growth

Myopia (short-sightedness), characterized by excessive ocular growth, is the most common visual disorder and is the greatest risk factor for blindness later in life, though its etiology is uncertain. We have previously suggested that ocular volume regulation is related to the rate of Retinal Ion-Driven fluid Efflux from the vitreous to the lymphatic sinusoids of the choroid, and predict that common clinically approved diuretics (amiloride, bumetanide, and furosemide) known to act on different ion exchanger and cation-chloride symporter mechanisms in retina and RPE would show differential, sign-dependent effects on refractive compensation to optical defocusing lenses that normally induce myopia and hyperopia (long-sightedness) in chick.

On day 5, 169 post-hatching chicks were intravitreally injected with 5 μL of either 1 mM amiloride (a potassium sparing diuretic that blocks sodium channels), bumetanide or furosemide (both loop diuretics that predominantly inhibit Na⁺/2Cl^-/K⁺ co-transporters) in DMSO vehicle, or DMSO carrier control only, and fitted with + 10D, -10D lens, or No Lens. After 4 days of rearing, biometric data were collected. Electroretinograms (ERGs; N = 3-4 per drug group) were recorded in No Lens animals to assess the effects of diuretics on retinal light responses, both acutely (day 5) and 96 h post-injection (day 9).

Furosemide and amiloride reduced myopia development following negative lenses, while bumetanide and amiloride suppressed hyperopia development in response to positive lenses. ERG waveforms demonstrated that retinal integrity was maintained following drug injection, with evidence of modulation of the strength of ON vs. OFF pathway signaling compared with DMSO.

Thus, diuretics that alter retinal function and associated ion-driven transretinal/RPE fluid efflux from vitreous to choroid inhibit the induction of defocus-induced refractive errors. This highlights the potential of diuretic-like agents for the therapeutic management of myopia and associated myopia-induced ocular pathology.