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D. A. Mauler, I. Semkova, M. Huemmeke, N. Kociok, A. M. Joussen; Severe Vascular Lesions and Neurodegeneration in Retina of Mice Following Elevated Intraocular Pressure (iop)-Induced Retinal Ischemia. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4419.
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As previously shown, ischemia and reperfusion in the murine retina leads to vascular degeneration comparable to those seen in human diabetic retinopathy. The relationship between severe neuro- and capillaries-degeneration in retina due to ischemia in this model has not been fully understood.
Transient elevated IOP was induced in C57Bl/6J mice through the insertion of a needle into the anterior chamber of the right eye connected to a saline column. Elevated IOP at 90 mm Hg was maintained for 90 minutes. An increase of the IOP was confirmed by measurement with a tonometer. Retinal reperfusion was reestablished, and the animals were killed 2 and 7 days after the injury. On H&E stained paraffin cross-sections retinal morphology was investigated. On paraffin sections apoptotic cells were detected by M30 CytoDeath antibody. The retinal vasculature was studied on flatmounts by labelling with Isolectin (IB4 Alexa Fluor®).
On H&E stained slices the ganglion cell layer of the IOP retina was discontinued or thinner than the ganglion cell layer of the control slices. The architecture of the ganglion cell layer and the integrity of the inner limiting membrane were disturbed in the damaged eyes. The morphology of the control eyes was normal. Many apoptotic cells, detected by CytoDeath antibody were present in the ganglion cell layer and outer nuclear layer 2 and 7 days after injury. Sections taken from the control eyes showed no presence of apoptotic cells. On retinal flatmounts the normal vascular structure was disturbed in injured eyes. Highly degenerated capillaries that were not perfused as well as regions with capillary loss were observed. We found cells with typical macrophage-like morphology in the extravasal area of the flatmounted retinae of eyes, which underwent an experimental increase of the IOP. These cells were not detected on control retinas. The vascular system of the control flatmounts was easily visible and had a normal structure.
Increasing the IOP leads to severe degeneration in the ganglion cell layer and disruption of the inner limiting membrane integrity. Many apoptotic cells were present in the photoreceptor layer. Neuronal degeneration was accompanied by severe capillary degeneration in the ischemic retinae. Inflammatory cells such as infiltrated macrophages may stimulate cell death signalling leading to capillary degeneration. All these changes are similar to degenerative developments in the vascular system of retinae affected by diabetic retinopathy.
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