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Jessica Ackert, Tamas Atlasz; Gap Junctions and Retinal Angiogenesis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):589.
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To study the role of gap junctions in the development of proliferative retinal disease.
A well-established mouse model of oxygen-induced retinopathy (OIR) was used to induce proliferative retinal disease (Smith et al 1994). Briefly, litters were exposed to hyperoxic conditions (75% oxygen) from post-natal day (PD) 7 through PD 12 causing retinal vaso-obliteration. The litters were returned to room air on PD 12. The right eye of the mouse pups received a 1 µl intravitreal injection of 500 micromolar of the global gap junctional blocker meclofenamic acid (MFA) on PD12 and 13 . The left eye served as an untreated control. The relative hypoxia of room air induces a neovascular response which is maximal at PD 17-19. The mice were sacrificed at that time point; retinas isolated, flat-mounted, and stained with the vascular endothelial marker lectin. Retinas were imaged with fluorescence and confocal microscopy and amount of vaso-obliteration and neovascularization quantified using a well-described and validated method (Stahl et al 2009).
Pups treated with MFA showed a significant reversal of vaso-obliteration. Specifically, we find a 72% reduction in the area of ischemia of MFA-treated eyes compared with the contralateral non-treated retinas (n=7 pups). Similarly, there is an 78% decrease in the amount of retinal neovascularization in MFA-treated retinas compared with non-treated retinas (n=7 pups).
Our results indicate that gap junctions play a significant role in the development of proliferative retinopathy. While further study is needed to delineate the role of individual connexins, our data suggests that blockade of gap junctions may be a theraputic target in the treatment of retinal neovascular disease.
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