Purchase this article with an account.
C.-M. Lin, E. B. Wolpert, S. Shanmugam, D. A. Antonetti, T. W. Gardner, S. F. Abcouwer; Different Effects of Minocycline and Doxycycline on Retinal Vascular Permeability and Neurodegeneration in Ischemia-Reperfusion. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3648.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The tetracycline derivative minocycline has been shown to inhibit microglial activation and reduce pro-inflammatory cytokine expression in an animal model of diabetic retinopathy. We investigated the effectiveness of minocycline on retinal vascular permeability and neurodegeneration using a retinal ischemia-reperfusion (IR) injury model. The effects of minocycline were compared to another commonly used tetracycline derivative, doxycycline.
Male Sprague-Dawley rats were treated by intraperitoneal injections with either minocycline or doxycycline (22.5 mg per kg) twice daily for 4 days. One day after the initial treatment, retinal ischemia was induced in one eye for 45 min. The contralateral eye served as the sham control. Three functional assays, Evan’s blue dye accumulation, DNA fragmentation and caspase-3 activity (DEVDase), were performed after 48 hr of reperfusion. Experiments were repeated using a direct ocular drug delivery. Minocycline or doxycycline (640 ng in 2 µl) was delivered by intravitreal injections 4 hr before and 1 hr after ischemia and the same functional assays were performed 24 hr after ischemia.
IR injury caused retinal Evan’s blue dye accumulation, which was reduced from 5.8-fold to 2.9-fold by intraperitoneal minocycline treatment. When delivered by intravitreal injection, minocycline completely inhibited IR-induced dye accumulation. No significant changes were observed in either DNA fragmentation or caspase-3 activity with either drug delivery route. In contrast, doxycycline administered systemically or ocularly had no effect on any experimental outcomes.
Minocycline effectively inhibited vascular permeability response to IR without affecting neurodegeneration, which demonstrated that these two processes are distinct. Although structurally similar, doxycycline exhibited no effect on vascular permeability or neurodegeneration. Minocycline may be considered as a potential treatment for eye diseases with increased vascular permeability, such as diabetic retinopathy.
This PDF is available to Subscribers Only