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F. Germain, R. Barhoum, P. Esteve, M. García–Hoyos, Y. Fermin, N. Forns, C. Ayuso, P. Bovolenta, P. de la Villa; Increased Expression of Secreted Frizzled Related Proteins Parallels the Extent of Retinal Degeneration in Two Different Mouse Models of Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5246.
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Purpose: Secreted Frizzled Related Proteins (SFRPs) are modulators of Wnt signaling, a pathway involved in many developmental and pathological processes. Alteration in SFRP expression have been reported in the retina of patients affected with Retinitis Pigmentosa (RP; IOVS, 2000, 41:1297). However, it is unclear whether this variation is a secondary event or has a tight correlation with the progression of the disease. To begin to address this question we asked whether changes in SFRP expression correlate with the temporal progression of the rod degeneration in rd1 and rd10 mice, two well established models for human RP, where a mutation in the rod–specific phosphodiesterase causes the loss of rod photoreceptors with a very different time course (fast in rd1; slow in rd10). Methods: The time course of retinal degeneration was evaluated in rd1 and rd10 mice at 12, 20, 30 and 40 postnatal (P) days by recording full field electroretinographic responses. In parallel, morphological alterations of the retinas were determined by immunohistochemistry using cell–type specific markers. The levels of Sfrp1 and Sfrp2 expression in the retina were analyzed by RT–PCR and in situ hybridization in littermates. Results were compared with those obtained in age–matched C57/bl6 mice, used as controls. Results: In rd1 mice, rod photoreceptor degeneration starts at P12 and is completed by P20 when no ERG response is observed. During this period, Sfrp1 and Sfrp2 expression increases, tightly following the degree of photoreceptor degeneration. As expected a slower degeneration was observed in rd10 mice, where photoreceptor loss begins at P20 and progresses until P40. As in rd1, increased expression of Sfrp1 and Sfrp2 closely correlated with the time course of photoreceptor degeneration. Conclusions: Our study provides further details on the time course of retinal degeneration in rd1 and rd10 mice and demonstrates that variations in Sfrp1 and Sfrp2 are directly related to the progression of the disease. We are currently addressing whether the increased expression of Sfrps might directly contribute to cell death.
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