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N. Tuntivanich, A.J. Weber, J.A. Render, S.M. Petersen–Jones; Histopathological Characterization of the Retinal Degeneration of the Rod Cyclic GMP Phosphodiesterase Alpha (PDE6A) Mutant Dog Model of Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5238.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To characterize histopathological changes at light and electron microscopic levels in the PDE6A mutant dog model of retinitis pigmentosa. Methods: Globes of PDE6A mutant, and breed and age matched normal control dogs were collected between 2 and 60 weeks of age. The medial half of the eyecup was fixed, plastic embedded and processed for light microscopy. Thickness of the retinal layers was measured at 8 regions along a vertical plane through the optic nerve head using Neurolucida software; v.3 (MicroBrightField, Inc). The lateral half was processed for transmission electron microscopy. Results: At 2 weeks of age in both mutants and controls photoreceptor inner segments (ISs) were present in all retinal regions and outer segments (OSs) had started to develop in the central retina. The OSs of the mutant dog were shorter than those of controls and reached their maximal length in the central retina at about 4 weeks of age and did not develop further. Additionally they were disoriented and had distortion of the discs. After 4 weeks of age the OS length of the mutant dogs progressively decreased whereas in the controls they continued to lengthen until reaching a maximum at about 7 weeks of age. Loss of OSs left stubby ISs. By 7 weeks of age the number of rows of photoreceptor nuclei in the central retina of mutant dogs was ∼6 rows compared to ∼11 rows in controls. At this age in mutant dogs there was relative preservation of cone nuclei compared to rod nuclei. By 16 weeks of age in the mutant dogs OSs had almost completely disappeared throughout the retina and ISs were only about 20% the length of control ISs. Three rows of photoreceptor nuclei remained compared to 11 rows in normal controls. Inner retinal layers were also thinned by this age. By 60 weeks of age a single layer of photoreceptor nuclei remained in some areas within the central retina but few were present in the periphery. The retinal thickness was ∼ 40% of that of controls with thinning of all layers. Conclusions: Photoreceptor OSs of the PDE6A mutant dog stop developing at an early age leaving stunted, distorted OSs with disorganized discs. These dysplastic photoreceptors progressively degenerate. Rods are rapidly lost whereas cone photoreceptors degenerate more slowly. There is an eventual thinning of all retinal layers.
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