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S.M. Petersen–Jones, M. Kiupel, A.J. Fischer, G. Omar, N. Tuntivanich; Immunohistochemical Characterization of Retinal Changes in the Rod Cyclic GMP Phosphodiesterase Alpha (PDE6A) Mutant Dog Model of Retinitis Pigmentosa . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5256.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate retinal changes in dogs with a retinal dystrophy due to a PDE6A mutation. Methods: The posterior eye cups from PDE6A mutant dogs and normal controls between 3 & 60 weeks of age were processed for immunohistochemistry and stained with antibodies to rhodopsin, red/green cone opsin, PKCα, calbindin, Hu, calretinin and GFAP. Results:Development of rhodopsin positive outer segments of mutant dogs was halted at 4 weeks of age and followed by a rapid loss, such that by 7 weeks of age there was very little rhodopsin positive outer segment material remaining. Red/green cone immunoreactivity persisted after the loss of rhodopsin immunoreactivity, although there was increasing mislocalization of expression to the cell bodies and synaptic processes, and loss of outer segments. The number of PKCα staining cells was decreased by 7 weeks of age and the cell processes and synaptic terminals disorganized. At this age there was also a decrease in the number of Hu positive cell bodies. Calretinin and calbindin staining was relatively well preserved in the inner retina, although the number of discrete cell bodies appeared to decrease. In the control dogs GFAP immunoreactivity was present predominantly in the nerve fiber layer and the outer portion of the inner nuclear layer. In the mutant dogs GFAP immunoreactivity was increased by 4 weeks of age, radiating from the inner to outer limiting membranes. Conclusions: Rod outer segment development in PDE6A mutant dogs becomes halted and is followed by a rapid loss of the rod cells. Cones positive for red/green opsin degenerate at a much slower rate with remaining cells showing mislocalization of opsin immunoreactivity suggesting they are perturbed by the loss of surrounding photoreceptors. Rod bipolar cell loss and altered pattern of cell processes and synapses follows the loss of rod photoreceptors. Other inner retinal cells are more slowly lost with ganglion cells, Hu positive and calretinin positive amacrine cells being lost prior to other inner retinal cells. The number of neuronal processes remaining in the inner retina appear proportionally greater than the number of surviving cell bodies perhaps indicating sprouting of additional cell processes from the remaining retinal cells. Activation of Müller cells is apparent from an early age, prior to substantial loss of photoreceptors.
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