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L. Zhao, Y. Li, Y. Song, Y. Liu, A. M. Laties, M. M. LaVail, R. Wen; CNTF Induces Regeneration of Cone Outer Segments in Transgenic Rats Carrying the Rhodopsin Mutation S334ter. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4502.
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In retinitis pigmentosa, loss of rods is followed by cone degeneration. In transgenic rats carrying the rhodopsin mutation S334ter (line 3), cones start to lose outer segments soon after the initiation of rod degeneration. The loss of cone outer segments is distributed ed in small patches. The present work examines the effect of CNTF on cones.
Recombinant human CNTF was delivered by intravitreal injection to animals from postnatal day 20 (PD20) to 6 months of age. The left eye of an animal was injected with CNTF (10 µg in 5 µl PBS), and the right eye with PBS (5 µl). Eyes were harvested 10 days after injection. Cone outer segments and cell bodies were identified by staining with peanut agglutinin lectin (PNA) and antibodies against rodent cone arrestin, respectively, in whole-mount retinas and examined by fluorescence confocal microscopy.
Loss of cone outer segments was evident as early as PD12, characterized by complete lack of PNA staining in small areas which formed round or irregularly shaped non-staining patches. The loss of PNA staining was progressive. In the patches, however, cone cells were still present, as demonstrated by the positive staining of cone arrestin. Surprisingly, CNTF treatment induced reappearance of PNA staining in previously non-staining patches, indicating regeneration of cone outer segments. As a result, the patches became smaller in size or even completely disappeared. In addition, CNTF prevented further loss of cone outer segments. The reappearance of PNA-positive cells induced by CNTF treatment was significant in animals from PD20 to 4 months of age.
CNTF promotes regeneration of outer segments in cones in early stages of cone degeneration.
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