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Joaquin De Juan, Jose R. Hombrebueno, Alicia Garcia-Alcazar, Jose L. Girela, Eun-Jin Lee, Norberto M. Grzywacz; The Matrix Metalloproteinase Inhibitor GM 6001 Impairs Cone Elongation, And Disrupts Cone Arrangement During Dark Adaptation In Teleost Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5430. doi: https://doi.org/.
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Inner and outer photoreceptor segments are surrounded by an interphotoreceptor matrix (IPM) located between the retinal outer limiting membrane and the apical border of the retinal pigment epithelium. This IPM realizes important functions for normal vision, such as maintain normal photoreceptor alignment. In turn, metalloproteinases (MMPs) and their inhibitors (MMP-I), play a central role in supporting retinal structure and function, by modulating the IPM. In teleost retinas cone arrangement change because the retinomotor movements. Thus, cones contract in light-adaption and elongate in darkness. The aim of this work is to observe the effects produced, after intraocular injection of a synthetic MMP-I (GM 6001), in the cone arrangement during light- and dark-adaptation.
The study was performed in Dicentrarchus labrax. We injected 10µl of GM 6001 (Working dilution 100nM en low salt buffer), into an eye, using the contralateral vehicle-injected eye as a control. After 24 h, light- and dark-adapted fishes were sacrificed and their retinas processed for transmission-electron-microscopy studies. Vertical and transversal semi-thin sections were obtained and observed with a light microscope and pictures obtained for morphometric studies.
Three main changes were observed in cone photoreceptors. First, in dark-adapted retinas, injected with GM 6001, numerous cones suffered a disruption of its normal vertical alignment, appearing oblique and horizontally orientated. Secondly, the typical cone myoide elongation, produced during dark-adaptation, was 20% lower in GM 6001 injected retinas than in control dark-adapted ones. Finally, light-adapted retinas injected with GM 6001, displayed normal cone contraction and ellipsoids located close to outer limitant membrane, in a similar way as control ones. However, inner and outer photoreceptor segments appeared surrounded by a wide vacuolated zone.
In teleosts retinas, interphotoreceptor matrix, metalloproteinases and their tissue inhibitors are necessary for a normal photoreceptor arrangement and cone retinomotor elongation in dark-adaptation.
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