The objective of this study is to analyze the structural characteristics of the retinal pigment epithelium (RPE) and retina of pearl mutant mice that could relate to the subnormal retinal sensitivity of the mutant. The immunolocalization of specific, well-characterized antisera directed against cytoskeletal components will be determined in the RPE of mutant and wild-type mice in order to identify components of the cytoskeleton associated with the basal surface of the RPE. The basement membrane (BM) of the RPE will be characterized by the immunolocalization of BM components and by the application of cationic dyes to assess the density and distribution of anionic binding sites. The chemical nature of the anionic binding sites will be determined by applying glucosaminoglycan degradative enzymes prior to the application of cationic dyes. The simultaneous application of two antisera will be used to determine cytoskeletal and basement membrane contacts. Cytoskeleton and basement membrane alterations are suggested as the cause of the structural anomalies of the basal surface of the mutant RPE, i.e., lack of basal infoldings and increased amount of basement membrane. These structural anomalies could affect RPE transport essential for the normal function of the retina. The immunolocalization of cytoskeletal components will also be determined in rod photoreceptor terminals of pearl mutant and wild-type mice. Cytoskeletal alterations in the mutant terminal could mediate alterations of synaptic lamellae structure. The modified synaptic lamellae of rod photoreceptors implicate the rod synaptic terminal as a possible site of altered synaptic transmission in the pearl mutant retina. Experiments will test whether the pearl mutant RPE influences the morphology of synaptic lamellae by observing lamellae in retinas of chimeric mice (+/+ leads to pe/pe) and pearl mutant mice which exhibit regions of reverse mutation (pe+/pe) in their RPE. An RPE influence would be demonstrated if modified synaptic lamellae were located solely in retinal areas underlying the pearl mutant RPE. The structural anomalies of the pearl RPE and retina are not unique characteristics of the pearl mutant but also are present in diseased and senescent human retinas, in diabetic BB rats and in rats with inherited retinal dystrophy. Thus, these investigations should give a better understanding of potential malfunctions of mammalian neural retina and pigment epithelium in general.
| Williams, M A; Pinon, L G; Linden, R et al. (1990) The pearl mutation accelerates the schedule of natural cell death in the early postnatal retina. Exp Brain Res 82:393-400 |
| Suzuki, H; Williams, M; Pinto, L H (1987) A method for explanting retina and retinal pigment epithelium of the mouse and culturing both tissues together. Prog Clin Biol Res 247:259-67 |
