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Manuel Rey-Funes, Verónica Berta Dorfman, Mariano Esteban Ibarra, Elena Peña, Daniela Soledad Contartese, Jorge Goldstein, Juan Manuel Acosta, Ignacio M. Larráyoz, Ricardo Martínez-Murillo, Alfredo Martínez, César Fabián Loidl; Hypothermia Prevents Gliosis and Angiogenesis Development in an Experimental Model of Ischemic Proliferative Retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(4):2836-2846. doi: 10.1167/iovs.12-11198.
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To develop a time course study of vascularization and glial response to perinatal asphyxia in hypoxic-ischemic animals, and to evaluate hypothermia as possible protective treatment.
We used retinas of 7-, 15-, 21-, and 30-day-old male Sprague-Dawley rats that were exposed to perinatal asphyxia at either 37°C (PA) or 15°C (HYP). Born to term animals were used as controls (CTL). We evaluated the thickness of the most inner layers of the retina (IR), including internal limiting membrane, the retinal nerve fiber layer, and the ganglion cell layer; and studied glial development, neovascularization, adrenomedullin (AM), and VEGF by immunohistochemistry, immunofluorescence, and Western blot.
A significant increment in IR thickness was observed in the PA group from postnatal day (PND) 15 on. This alteration was concordant with an increased number of new vessels and increased GFAP expression. The immunolocalization of GFAP in the internal limiting membrane and perivascular glia of the IR and in the inner processes of Müller cells was coexpressed with AM, which was also significantly increased from PND7 in PA animals. In addition, VEGF expression was immunolocalized in cells of the ganglion cell layer of the IR and this expression significantly increased in the PA group from PND15 on. The retinas of the HYP group did not show differences when compared with CTL at any age.
This work demonstrates that aberrant angiogenesis and exacerbated gliosis seem to be responsible for the increased thickness of the inner retina as a consequence of perinatal asphyxia, and that hypothermia is able to prevent these alterations.
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