Purpose: 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. Methods: 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. Results: 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