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K. A. Wunderlich, J. Sancho-Pelluz, F. J. Romero, T. van Veen, M. T. Perez; Induction of Metallothionein I/II Accompanies Photoreceptor Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4487.
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© ARVO (1962-2015); The Authors (2016-present)
Metallothionein I/II (MT-I/II), cystein-rich proteins that participate in the regulation of cellular zinc signaling systems, are up-regulated in response to increased levels of e.g., oxyradicals and pro-inflammatory cytokines. The purpose of the present study was to examine the temporal expression of MT-I/II in different rodent models of Retinitis Pigmentosa.
The distribution of MT-I/II was analyzed by immunohistochemistry in retinas obtained from rd1 mice, postnatal days 7 to 21 (P7-P21), rds mice (P8-P30), and RCS (Royal College of Surgeon) rats (P8-P42). Specific markers of retinal cell types and structures (cellular retinal-binding protein, CRALBP; glial fibrillary acidic protein, GFAP; and CD11b) were used to identify cells expressing MT-I/II.
In normal rat and mouse retinas, expression of MT-I/II was observed in retinal pigment epithelium (RPE) at all ages examined. In rd1 mice, weakly labeled microglial cells were observed in the inner central retina at P11 and in the outer nuclear layer from P12 and onwards. Distinct labeling of Müller cells was also seen in rd1 mouse retinas, initially in the central retina (P12), followed by labeling also in the peripheral retina with increasing age. In rds mouse retinas, MT-I/II expression was also observed in Müller cells in the central retina at P16, but throughout the retina already at P18. In RCS rat retinas, labeling in Müller cells was also observed in central and peripheral retinas, but not until P32.
Up-regulation of MT-I/II is observed in glial elements in association with photoreceptor degeneration. In rd1 mice, the increase in MT-I/II expression seems to closely parallel the center-to-periphery degeneration of rod photoreceptors. In rds mice, expression occurs throughout the retina but is also observed at early time points. These observations suggest that MT-I/II is induced as part of an early endogenous rescue response triggered by the initial cellular stress and ongoing degeneration. On the other hand, in RCS rats, considerable photoreceptor cell loss occurs before MT-I/II levels appear elevated, suggesting that MT-I/II induction is associated rather with events secondary to the photoreceptor cell loss.
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