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C. Dot, F. Behar-Cohen, D. BenEzra, L. Jonet, F. May, J.-C. Jeanny; Effects of Intravitreal -Aminoadipic Acid Injection on Retinochoroidal Healing Processes After Argon Photocoagulation in C57bl/6j Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3413.
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Disturb the normal glial function with an α-aminoadipic acid (AAA) intravitreal injection and analyse ist potential effects on the wound healing processes after photocoagulation (PC), in a well established mouse model of choroidal neovasculization (CNV).
Wild type C57BL/6J mice, 10 to 12 week old underwent firts an AAA intravitreal injection then a standard PC. They were divided in four groups : group I (n=2), group II (n= 10), group III (n=7), these mice received respectively 10mM, 50mM, and 100mM of AAA, and group IV (n=6) : these are the control mice without PC but injected with 50 and 100mM. Three weeks later, the usual argon laser PC protocol was performed. Two photocoagulation impacts (50µm, 400mW, 0,05s) were created two disc diameters from the optic nerve in both eyes. Two weeks after PC, the totality of the animals were sacrified, except 2 animals of the group II and III which were sacrified later, 2 months after PC. The eyes were mounted in Tissue tek (OCT), snap frozen and processed for immuno-histochemistry. Specific antibodies against GFAP, von Willebrand (vW) factor, were used respectively for the labelling of astrocytes and Müller’s cells, and vascular endothelial cells. DAPI staining was also carried out in order to localise the inner and outer nuclear layers and was associated with Tunel reaction too.
In Group I, low doses of αAAA affect partially the Müller cells and surprisingly the photoreceptors too. At this doses CNV can occur on day 14, as usual in this experimental model after PC. In Group II, αAAA affects markedly the Müller cells and CNV reaction is clearly reduced but not completely inhibited. Moreover we can observe localized serous detachment in the retina. The analysis of the group III was reduced by the fact of poor usable samples. At this dose αAAA appears to be toxic for retina. On day 14, a large part of the eyes were affected by sub or total retinal detachment and PC could not be performed because of these vitreoretinal complications. Elsewhere retina appeared atrophic.
αAAA up to 50µg, is rapidly toxic. This highlights the architectural role of glial cells in the retina. This toxin does not affect specifically Müller cells but part of the photoreceptors too . Glial cells damage reduces CNV reaction. This supports the role of gial cells in the complex cellular reactions leading to CNV.
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