Retinal degeneration in the nervous mutant mouse. IV. Inner retinal changes.

We have recently noted that the inner nuclear layer (INL) and the inner plexiform layer (IPL) were significantly thinner in mice homozygous for the nervous defect (nr / nr) than in control (nr /+ or +/+) littermates. Here, we have carried out a series of anatomical studies to further understand these inner retinal changes. At postnatal day (P) 13, there was no difference in the inner retina between nervous and control mice, while a significant difference was observed at P30. Similar changes were not seen in other mouse models of photoreceptor degeneration. There was a significant reduction in the density of cells in the INL that were stained by antibodies against the inhibitory neurotransmitters GABA and glycine. These results indicate that the nervous defect causes a degeneration of one or more sub-types of amacrine cells, in addition to the loss of cerebellar Purkinje cells and retinal photoreceptors that is known to occur in these mutant animals. Finally, evidence is provided that photoreceptors die by an apoptotic pathway in nervous mice.

[1]  A. Y. Chow,et al.  Subretinal implantation of semiconductor-based photodiodes: progress and challenges. , 1999, Journal of rehabilitation research and development.

[2]  A. Milam,et al.  Apoptosis in Retinitis Pigmentosa , 1995 .

[3]  R. J. Mullen,et al.  Retinal degeneration in the nervous mutant mouse. I. Light microscopic cytopathology and changes in the interphotoreceptor matrix , 1993, The Journal of comparative neurology.

[4]  A. Milam,et al.  Light-induced acceleration of photoreceptor degeneration in transgenic mice expressing mutant rhodopsin. , 1996, Investigative ophthalmology & visual science.

[5]  P. Röhlich,et al.  Degeneration of Cone Photoreceptors Induced by Expression of the Mas1 Protooncogene , 2000, Experimental Neurology.

[6]  Y. Hao,et al.  Apoptosis: Final common pathway of photoreceptor death in rd, rds, and mutant mice , 1993, Neuron.

[7]  M. Lavail,et al.  Degenerative Diseases of the Retina , 2012, Springer US.

[8]  P. Röhlich,et al.  A 221-bp fragment of the mouse opsin promoter directs expression specifically to the rod photoreceptors of transgenic mice , 1997, Visual Neuroscience.

[9]  S. Ball,et al.  Successful cotransplantation of intact sheets of fetal retina with retinal pigment epithelium. , 1999, Investigative ophthalmology & visual science.

[10]  A. Bird,et al.  An immunohistochemical study of an autosomal dominant feline rod/cone dysplasia (Rdy cats). , 1999, Experimental eye research.

[11]  H. Wässle,et al.  Glycine and GABA receptors in the mammalian retina , 1998, Vision Research.

[12]  R. J. Mullen,et al.  Two new types of retinal degeneration in cerebellar mutant mice , 1975, Nature.

[13]  M. Lavail,et al.  Degenerative Retinal Diseases , 2012, Springer US.

[14]  A. Cideciyan,et al.  Clinicopathologic effects of the Q64ter rhodopsin mutation in retinitis pigmentosa. , 1996, Investigative ophthalmology & visual science.

[15]  M. Lavail,et al.  Retinal degeneration in the nervous mutant mouse. III. Electrophysiological studies of the visual pathway. , 2000, Experimental eye research.

[16]  A. Bird,et al.  A 3-bp deletion in the rhodopsin gene in a family with autosomal dominant retinitis pigmentosa. , 1991, American journal of human genetics.

[17]  E. Mugnaini,et al.  Effects of the murine mutation ‘nervous’ on neurons in cerebellum and dorsal cochlear nucleus , 1988, Journal of neurocytology.

[18]  S. Landis.  ULTRASTRUCTURAL CHANGES IN THE MITOCHONDRIA OF CEREBELLAR PURKINJE CELLS OF NERVOUS MUTANT MICE , 1973, The Journal of cell biology.

[19]  Zy Li,et al.  Rod photoreceptor neurite sprouting in retinitis pigmentosa , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[20]  A re‐examination of anatomical plasticity in the rat retina , 1976, The Journal of comparative neurology.

[21]  J. Nathans,et al.  Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[22]  S. Landis.  Changes in neuronal mitochondrial shape in brains of nervous mutant mice. , 1973, The Journal of heredity.

[23]  R. J. Mullen,et al.  Retinal degeneration in the pcd cerebellar mutant mouse. I. Light microscopic and autoradiographio analysis , 1982, The Journal of comparative neurology.

[24]  A. Milam,et al.  Preservation of the inner retina in retinitis pigmentosa. A morphometric analysis. , 1997, Archives of ophthalmology.

[25]  R. J. Mullen,et al.  Purkinje cell degeneration, a new neurological mutation in the mouse. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[26]  N. Heintz,et al.  A high-resolution genetic map of the nervous locus on mouse chromosome 8. , 1998, Genomics.

[27]  J. Lavail,et al.  Assessment of possible transneuronal changes in the retina of rats with inherited retinal dystrophy: Cell size, number, synapses, and axonal transport by retinal ganglion cells , 1984, The Journal of comparative neurology.

[28]  M. Naash,et al.  Simulation of human autosomal dominant retinitis pigmentosa in transgenic mice expressing a mutated murine opsin gene. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[29]  R. J. Mullen,et al.  Retinal degeneration in the nervous mutant mouse. II. Electron microscopic analysis , 1993, The Journal of comparative neurology.

[30]  A. Milam,et al.  Rhodopsin transgenic pigs as a model for human retinitis pigmentosa. , 1998, Investigative ophthalmology & visual science.

[31]  A. Milam,et al.  Abnormalities in rod photoreceptors, amacrine cells, and horizontal cells in human retinas with retinitis pigmentosa. , 2000, American journal of ophthalmology.