Metipranolol is a β-
adrenergic receptor antagonist that is given orally for the treatment of
hypertension and also applied topically to the cornea for treating
glaucoma. It also inhibits nitrosative stress which has previously been shown to be the cause of cone photoreceptor death in
retinitis pigmentosa. In this study, we tested the hypothesis that
metipranolol protects photoreceptor structure and function in the mouse model rd10. At P35, compared with vehicle-treated rd10 mice in which rod degeneration was nearly complete, rd10 mice given daily
subcutaneous injections of 40 mg/kg of
metipranolol had reduction in markers of nitrosative stress, fewer TUNEL-positive cells, increased outer nuclear layer thickness, and substantially more staining for
rhodopsin. This was accompanied by significantly higher mean scotopic and photopic electroretinogram b-wave amplitudes indicating improved photoreceptor function. At P50,
metipranolol-treated rd10 mice had decreased
3-nitrotyrosine staining in the retina, increased immunostaining for cone
arrestin, a marker for cone photoreceptors, and significantly higher scotopic and photopic b-wave amplitudes at the highest stimulus intensity compared with vehicle-treated mice. At P65, cone density was significantly higher in
metipranolol-treated versus vehicle-injected rd10 mice.
Metipranolol applied as
eye drops promoted cone photoreceptor function in retinas of rd10 mice greater than subcutaneously injected
metipranolol. The reduced nitrosative damage and rescue of functional loss of photoreceptors in rd10 mice suggests that
metipranolol, a drug with established ocular safety and tolerability, may have potential for treating patients with
retinitis pigmentosa.