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Pilar Villacampa, Virginia Haurigot, Albert Ribera, Laura Ramirez, Pedro de la Villa, Fatima Bosch; Neurophysiological Alterations in Transgenic Retinas Overexpressing IGF-I. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5967.
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To determine the compromise of neuronal function in transgenic mice over expressing Insulin-like Growth Factor (TgIGF-I) in the retina. Previous studies have shown that TgIGF-I have retinal alterations characteristic of non-proliferative retinopathy and, with age, develop alterations that mimic the proliferative stage of the disease, such as retinal neovascularisation.
Flash electroretinographic (ERG) responses were recorded under dark and light adaptation in TgIGF-I and wild type (WT) mice at 3, 6, 7.5 and 9 months of age, and the amplitudes or the a- and b-waves of the ERG responses were compared. Flash intensities ranged from -4 to 2 log cd·s·m-2. Inmunohistochemistry for a series of retinal neuronal markers was performed in paraffin-embedded retinal sections, and neuronal populations were determined by morphometric analysis. Western blot analysis was also performed in retinal protein extracts from TgIGF-I and WT mice of different ages.
No differences were observed between TgIGF-I and WT in the ERG responses recorded in 3 months-old mice, in neither scotopic nor photopic conditions. At 6 months of age, abnormal responses were detected in several TgIGF-I mice. By 7.5 months of age, the ERG amplitudes of all TgIGF-I mice showed statistically significant differences when compared to WT animals, with a reduction greater than 50% in amplitudes of both a and b-waves for all intensity ranges. Histological analysis showed a decrease in bipolar cell and ganglion cell populations in 7.5 months-old TgIGF-I mice. Moreover, at this age, the outer segments of rod photoreceptors showed a significant decrease in length in transgenic mice. Western blot analysis confirmed reduced levels of neuronal markers in retinal extracts.
Transgenic mice with retinal overexpression of IGF-I present a significant reduction in retinal neuronal function with age. Furthermore, a substantial decrease in retinal cell populations parallels the decrease in the ERG responses. The pathological alterations observed in the TgIGF-I mice are concomitant with retinal neovascularization, vascular leakeage and glial activation. We propose that these factors may be involved in the neuronal damage of this mouse model of retinal disease.
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