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María Paz Villegas-Pérez, Johnny Di Pierdomenico, Diego Garcia-Ayuso, Manuel Jimenez-Lopez, Ana María Gómez-Ramírez, Marta Agudo-Barriuso, Manuel Vidal-Sanz; Repeated intravitreal injections cause stronger microglial and macroglial reactions than single injections. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2676.
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© ARVO (1962-2015); The Authors (2016-present)
Single or repeated intravitreal injections of anti-VEGF and triamcinolone are used to treat various retinal diseases. We have investigated the retinal glial responses after one or three injections of these substances or their respective vehicles.
Adult albino Sprague-Dawley (SD) rats (n=6) received in the left eye 1 or 3 weekly intravitreal injections of 5 µl of bevacizumab (25 µg/µl; Avastin®, Roche Farma), anti-rat VEGF (0.015 µg/µl; VEGF, MGC70609, Leinco Technologies) or 2.5 or 5 µl of triamcinolone acetonide (40 µg/µl; Trigón Depot® Bristol-Myers Squibb) or their vehicles: PBS or BSS® (Alcon). Seven days after the single or the last injection the retinas were processed as wholemounts and immunoreacted with a mixture of antibodies: anti-Iba1+anti-GFAP or anti-Vimentin+anti-GFAP. Macroglial cells were analysed qualitatively and microglial cells were quantified with semi-automatic methods in 12 standard areas (3 mm2) of each retina.
A local intense glial response was always observed around the injection site. In addition, a generalized glial response was also observed that varied depending on the substance and number of injections. One injection of bevacizumab caused such a strong microglial reaction that the numbers of microglial cells could not be quantified, while the rest of the substances as well as the corresponding vehicle solutions increased significantly the numbers of microglial cells in the injected retinas but not in the contralateral retinas. Three injections of anti-rat VEGF, triamcinolone or their vehicles caused a significantly stronger microglial reaction than a single one. Macroglial hypertrophy was observed in all the injected retinas. Other macroglial alterations, such as local increases in GFAP immunoreactivity were only observed in groups receiving triamcinolone and/or 3 injections of any substance and were located at the end feet of Müller cells.
Single and repeated intravitreal injections of pharmacologic substances and/or their vehicles cause local effects on the macroglial and microglial retinal cells in the injected retinas. These effects depend on the substance injected and/or the number of injections. Further studies are required to show whether they are detrimental or beneficial for the diseased retina.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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