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mara albert, Sheila Pons-Vazquez, Jose M. Romero, SILVIA SANZ-GONZALEZ, Deborah Burks, Maria D. Pinazo-Duran; Changes in insulin receptor substrate 2 (IRS-2) alter the retinal morphology and dynamics in relation to Diabetes Mellitus. Invest. Ophthalmol. Vis. Sci. 2012;53(14):783.
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© ARVO (1962-2015); The Authors (2016-present)
Insulin receptor substrate (IRS-2) mediates peripheral insulin action and pancreatic b-cell function. Changes in IRS-2 induce diabetes in mice. We evaluate the role of IRS-2 in the retinal cytoarchitectural dynamics, in relation to insulin resistance and diabetic retinopathy.
Adult mice of the C57BL/6 strain, were divided into two groups: 1) IRS 2 lacking (IRS2 -/-; n=22), 2) wild type (wt; n= 20). Animals were sacrificed according to the ARVO guidelines. Eyes were micro-dissected and frozen. Immunohistochemical staining in either cryostat transverse eyeball sections or whole-mount retinas were performed using GAD 67, parvalbumin, caldendrin, calretinin and Gly T1 as primary antibodies that reacted with fluorescently labelled secondary antibodies. Fluorochromes were Alexa 488, Cy3, and Cy5. Preparations were examined with confocal microscope equipped with a krypton/argon laser (Zeiss, LSM 410). Images were adjusted using Adobe Photoshop 5.5. Data were processed by the SPSS 15.0 program.
IRS2-/- retinas displayed significantly lower retinal thickness and layering than the wt (p<0.001). Substantial dysregulation of GAD 67, parvalbumin, caldendrine, calretinine and Gly T1 expression were observed in amacrine and ganglion cells of the IRS2-/- retinas. Topographies of the immunoreactive retinal cell populations were quantified in both groups and a significant decrease in amacrine (p<0,001) and ganglion cell (p<0,001) density was detected in the IRS2 -/- eyes.
IRS2 deficiency alters retinal amacrine and ganglion cells morphology and dynamics, probably by interfering with cell cycle mechanisms and/or essential survival signaling pathways. Amacrine and ganglion cells are closely involved in pathogenesis of ongoing diabetic retinopathy.
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