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Editors Selection IGR 15-3

Medical Treatment: Investigational eyedrops

Comment by Louis Pasquale on:

54424 17β-estradiol eye drops protect the retinal ganglion cell layer and preserve visual function in an in vivo model of glaucoma, Prokai-Tatrai K; Xin H; Nguyen V et al., Molecular pharmaceutics, 2013; 10: 3253-3261

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Considerable evidence already exists that estrogen is a viable target in the treatment of glaucoma. This study involved ovariectomized (OVX) rats ‐ male rats and female rats with intact ovaries were not studied. The researchers show that estrogen can be detected in the retina of OVX rats but that topical application of 17β-estradiol (E2) 0.05% once daily produced marked increases in the local concentration of this hormone in the cornea, lens and retina. Furthermore, augmentation of retinal estrogen levels with topical E2 was associated with increased expression of proteins linked to retinal ganglion cell survival such αA and βB-crystallins. Bilateral ocular hypertension was induced in OVX rats by sclerosing the episceral veins and after approximately seven days one eye was treated with E2 0.05% once daily for 19 days while the fellow eye received vehicle. While topical E2 had no effect on intraocular pressure, its use was associated with a 50% reduction in TUNNEL positive retinal ganglion cells compared to the contralateral control eye. Details regarding tissue sampling and whether these assessments were made masked are not provided.

Estrogen: a new therapeutic target for glaucoma?

Furthermore neither retinal ganglion cells nor their axons were counted, but the authors did assess the effect of treatment on visual function. The E2-treated eye of OVX rats with glaucoma had significantly improved contrast sensitivity compared to the control eye as determined by masked observers. Topical E2 drops did enter the systemic circulation and resulted in significant uterine hypertrophy. This study provides strong evidence that topical E2 is neuroprotective in a rodent model of glaucoma. Future efforts should be directed toward leveraging the potential therapeutic effects of E2 on the optic nerve while reducing unwanted systemic effects.

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