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Jesus Fraile Maya, Ricardo Romero Martín, Jose Carretero Gonzalez, Pino Cidad Betegon; IRS-2 NECESSARY FOR STRUCTURAL ORGANIZATION OF THE RETINA. Invest. Ophthalmol. Vis. Sci. 2018;59(9):5369. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Knock out mice for IRS2 show alterations of the development in the retina and neurodegenerative processes with the age.We want to confirm the role of this protein in the establishment of retinal pathology and retinal degenerative processes.Objective: to analyze if the absence of IRS2 affects other layers of the retina other than the photoreceptors, if there are structural abnormalities and neuronal distribution, if there is retinal reactive gliosis, if amacrine cells are affected and if there is apoptosis.
Twenty male 12-week old mice, 10 wilde type and 10 knock out for IRS2 are employed. At 20 days of age genotyping is performed by PCR. At 12 weeks the mice are sacrificed and 5 micron thick sections are obtained for the histochemical-morphometric study (Mayer's hematoxylin) and immunocytochemistry (anti-GFAP antibodies, anti-vimentin, anti-glutamine synthetase, anti-tyrosine hydroxylase, active anti-caspase 3).
Morphometric analysis shows that the retinal thickness of the knock out mice is significantly less thick than that of the wilde type mice.The absence of IRS2 induces the appearance of a retinal degeneration not linked to hyperglycemia or to vascular alterations, which diffusely affects the retina.This retinal degeneration is accompanied by non-inflammatory reactive gliosis with increased expression of GFAP and vimentin in astrocytes.There is a clear decrease in Müller cells and a decrease in positivity to glutamine synthetase, decreasing the metabolism of glutamate, favoring its neurotoxic effect.Increased expression of Aromatase P-450, suggesting an increase in local synthesis of estradiol as an attempt to maintain a neuroprotective effect.It clearly decreases dopaminergic activity and amacrine cells, suggesting that the system of adaptation to light intensity is seriously affected.The absence of IRS2 is an apoptotic stimulus in the deep neural zone of the retina.
This is the first study to analyze the effects of the absence of the substrate protein IRS2 on the expression of vimentin, aromatase and tyrosin hydroxylase in the mouse retina.The absence of IRS2 affects other layers of the retina other than the photoreceptors.The absence of IRS2 induces retinal reactive gliosis and amacrine cells are affected and the end result is the activation of apoptosis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
General appearance central retina knock out mice
Immunocytochemical staining with vimentin
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