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S. K. Fisher, M. R. Verardo, J. Byun, G. P. Lewis, G. Luna, S. Kjellstrom, P. Sieving; Retinal Changes Following Experimental Retinal Detachment in the Retinoschisin Knockout Mouse. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1538.
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The retinoschisin knockout (RSKO) mouse is a model for the human disease of X-linked retinoschisis in which congenital delamination occurs through multiple retinal layers. A possible treatment for this disease involves the subretinal injection of viral vectors carrying the normal RS gene. Since this treatment approach creates a retinal detachment, we sought to determine the effects of detachment in RSKO mice.
Detachments were made in the right eyes of RSKO and wild-type (WT) mice by injecting saline between the RPE and neural retina. The left eyes served as controls. Eyes were removed 7 days post-detachment fixed, embedded and sectioned at 100 microns. Immunohistochemistry was performed using antibodies to rod opsin, neurofilament, GFAP and vimentin, and the tissue was analyzed by confocal microscopy. The size and number of retinal lamellar spaces, the number of subretinal glial scars, and the number of photoreceptor nuclei were quantified.
From previous work it is known that mouse retinas detached with saline will reattach spontaneously within 24 hr; therefore all retinas in this study are considered detached for 1 day followed by 6 days of reattachment. In the control eyes from the RSKO mice, the number of photoreceptor nuclei was consistently reduced compared to WT mice (42,704/mm sq vs. 45,282, p <0.006); there were numerous retinoschisis cavities throughout the inner nuclear layer (INL); the Mueller cells showed heightened reactivity evidenced by an upregulation of GFAP and vimentin immunolabeling and growth into the subretinal space; and neurite outgrowth from horizontal cells was observed. Following detachment/reattachment in the RSKO animals, there was a slight further decline in the number of photoreceptors by comparison to control RSKO mice (41,454 vs. 42,704); the number of cavities in the INL did not change, however, their average area (normalized to the area of the INL) was reduced by 20% (p<0.0007); the number of subretinal scars was not increased (3.4/mm); and neurite outgrowth from horizontal cells did not appear accentuated.
These data indicate that short term (1-day) detachments in RSKO mice followed by a period of reattachment does not accentuate the damage to the retina already underway due to the aberrant RS gene and may in fact reduce the size of existing retinal lamellar cavities. This suggests that performing a subretinal injection for the delivery of therapeutic agents may be a viable option in the treatment of retinoschisis.
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