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L. Luo, R. Wen, D. Huang, G. Gaidosh, Y. Li; Morphological Changes of Cone Photoreceptors During Rod Degeneration in the S334ter Transgenic Rats Carrying the Rhodopsin Mutation S334ter. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4468.
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© ARVO (1962-2015); The Authors (2016-present)
In the transgenic rats carrying the rhodopsin mutation S334ter, rod degeneration begins as early as postnatal day (PD) 8 and by PD 20, the degeneration is almost complete. The present work studies morphological changes of cone photoreceptor during rod degeneration in this animal model.
Cone morphology was studied at PD 8, 10, 12, 14, 16, 18, 20, 30, and 60 in homozygous S334ter-3 rats. At a given time point, animals were killed by CO2 overdose and perfused with 4% paraformaldehyde. Eyes were harvested and the anterior section, including the cornea, the iris, and the lens, removed. The resulted eye cups were then embedded in 5% agarose and vibratome sections (100 µm) were obtained. Tissue sections were stained with antibodies against blue opsin, which not only stains the blue cone outer segments (OS), but also the entire blue cone cells. Cone morphology was examined by confocal microscopy.
At PD 8, when the outer nuclear layer (ONL) had more than 10 rows of nuclei, cone cells had the normal elongated morphology and a "stand up" orientation. Starting at PD 10, the cell length of cones became shorter, characterized by the shortening of both the inner segments (IS) and the synaptic terminals. No significant changes occurred to the cell body where the nucleus resides. The OS becomes bent, away from the cell axis. By PD 12, the OS of many cones becomes horizontal, parallel to the subretinal space plane and 90° to the cell axis. As rod degeneration progresses and the ONL becomes thinner, the IS and the synaptic terminals become shorter, while the morphology of the cell body remains relatively unchanged. The cells retain their original orientation until PD 30 when they started to "lie down". By PD 60, most cones are oriented horizontally, taking a position parallel to the subretinal space plane.
Cone cells undergo dramatic morphological changes during rod degeneration, likely due to the thinning of the ONL and collapse of the subretinal space suggesting the importance of the physical support of rods in normal cone morphology.
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