Superior colliculus responses to light - preserved by transplantation in a slow degeneration rat model.

PURPOSE To determine whether retinal transplantation can preserve visual responses in the superior colliculus (SC) of the S334ter-line-5 rat, a transgenic model for slow photoreceptor degeneration, which is more similar to human retinitis pigmentosa than the fast degeneration line 3 S334ter rat. METHODS Visual responses to a light flash were recorded in the SC. Rats that had received embryonic day (E) 19-20 fetal retinal sheet transplants at the age of 26-30 days were tested at the ages of 200-254 days. Controls were age-matched rats without surgery and with sham surgery. As a baseline, in no-surgery line-5 rats, the temporal pattern of visual sensitivity loss was evaluated electrophysiologically in the SC from 60 days up to one year of age. RESULTS In untreated S334ter-line-5 rats, decline in visual sensitivity in the SC was parallel to the photoreceptor loss. At 109 day of age, a relative scotoma developed in the area of the SC corresponding to the nasal retinal region. At 200-254 days of age, the majority of the SC was devoid of any light-driven responses. In contrast, at this time point, transplanted rats with 'good' retinal grafts with normal lamination had visual responses in the caudal region of the SC, the area corresponding topographically to the transplant location in the retina. In these rats, the various parameters of SC responses such as the latency of the onset of the visual response, the response peak amplitude and the consistency of the visual response were significantly different from the control groups (no-surgery, sham surgery, 'poor' transplants) and were more comparable to normal albino rats, however, with a slightly longer latency (70-90 vs. 30-50 msec). CONCLUSIONS Fetal retinal sheet transplantation showed a long-term rescue effect on visual function in this animal model of slow photoreceptor degeneration.

[1]  C. Gravel,et al.  Adenovirus-mediated gene transfer of ciliary neurotrophic factor can prevent photoreceptor degeneration in the retinal degeneration (rd) mouse. , 1997, Human gene therapy.

[2]  Rhodopsin topography and rod-mediated function in cats with the retinal degeneration of taurine deficiency. , 1987, Experimental eye research.

[3]  R. Sidman,et al.  Congenic strains of RCS rats with inherited retinal dystrophy. , 1975, The Journal of heredity.

[4]  M. Silverman,et al.  Photoreceptor transplants increase host cone survival in the retinal degeneration (rd) mouse. , 1997, Ophthalmic research.

[5]  C. Núñez‐Álvarez,et al.  Experimental Eye Research , 2019, Nature.

[6]  J E Turner,et al.  Inherited retinal dystrophy in the RCS rat: prevention of photoreceptor degeneration by pigment epithelial cell transplantation. , 1988, Experimental eye research.

[7]  K Heimann,et al.  Rescue effects of IPE transplants in RCS rats: short-term results. , 1999, Investigative ophthalmology & visual science.

[8]  M. McCall,et al.  Retinal transplantation-induced recovery of retinotectal visual function in a rodent model of retinitis pigmentosa. , 2003, Investigative ophthalmology & visual science.

[9]  P. Gouras,et al.  Transplanted retinal pigment epithelium modifies the retinal degeneration in the RCS rat. , 1989, Investigative ophthalmology & visual science.

[10]  D. Hubel,et al.  Studies of visual function and its decay in mice with hereditary retinal degeneration , 1978, The Journal of comparative neurology.

[11]  M. Lavail,et al.  Basic fibroblast growth factor and local injury protect photoreceptors from light damage in the rat , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  R. Allikmets Molecular Genetics of Age-Related Macular Degeneration: Current Status , 1999, European journal of ophthalmology.

[13]  M. Lavail,et al.  Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

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

[15]  B. Jones,et al.  Neural remodeling in retinal degeneration , 2003, Progress in Retinal and Eye Research.

[16]  R. Aramant,et al.  Intact sheets of fetal retina transplanted to restore damaged rat retinas. , 1998, Investigative ophthalmology & visual science.

[17]  A. Adolph,et al.  Function and Structure in Retinal Transplants , 1994, Journal of neural transplantation & plasticity.

[18]  B. Jones,et al.  Retinal remodeling triggered by photoreceptor degenerations , 2003, The Journal of comparative neurology.

[19]  R. Lund,et al.  Progressive visual sensitivity loss in the Royal College of Surgeons rat: perimetric study in the superior colliculus , 2001, Neuroscience.

[20]  A. Moore,et al.  Genetic susceptibility to age related macular degeneration , 2000, Journal of medical genetics.

[21]  A. Milam,et al.  Morphometric analysis of the extramacular retina from postmortem eyes with retinitis pigmentosa. , 1999, Investigative ophthalmology & visual science.

[22]  M. Lavail,et al.  Photoreceptor degeneration in inherited retinal dystrophy delayed by basic fibroblast growth factor , 1990, Nature.

[23]  S. Ball,et al.  Photoreceptor function of retinal transplants implicated by light-dark shift of S-antigen and rod transducin , 1999, Vision Research.

[24]  T. Léveillard,et al.  Normal retina releases a diffusible factor stimulating cone survival in the retinal degeneration mouse. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[25]  R. Aramant,et al.  Retinal transplantation—advantages of intact fetal sheets , 2002, Progress in Retinal and Eye Research.

[26]  D. G. Green,et al.  Cone inputs to ganglion cells in hereditary retinal degeneration. , 1979, Science.

[27]  J. Bennett,et al.  Gene therapy and animal models for retinal disease. , 2003, Developments in ophthalmology.

[28]  R. Lund,et al.  Cell Transplantation as a Treatment for Retinal Disease , 2001, Progress in Retinal and Eye Research.

[29]  T. Muramatsu,et al.  Rescue of photoreceptors from the damaging effects of constant light by midkine, a retinoic acid-responsive gene product. , 1994, Investigative ophthalmology & visual science.

[30]  S. E. Hughes,et al.  Transplantation of photoreceptors to light-damaged retina. , 1989, Investigative ophthalmology & visual science.

[31]  P. Rakoczy,et al.  Retinal GFAP and bFGF expression after multiple argon laser photocoagulation injuries assessed by both immunoreactivity and mRNA levels. , 1997, Experimental eye research.

[32]  M. Lavail,et al.  Protection of mouse photoreceptors by survival factors in retinal degenerations. , 1998, Investigative ophthalmology & visual science.

[33]  You-Wei Peng,et al.  Ectopic synaptogenesis in the mammalian retina caused by rod photoreceptor-specific mutations , 2000, Nature Neuroscience.

[34]  R. Sidman,et al.  Differential effect of the rd mutation on rods and cones in the mouse retina. , 1978, Investigative ophthalmology & visual science.

[35]  L. Kruger,et al.  An electrophysiological study of the visual projection to the superior colliculus of the rat , 1966, The Journal of comparative neurology.

[36]  R. Aramant,et al.  Fiber and Synaptic Connections between Embryonic Retinal Transplants and Host Retina , 1995, Experimental Neurology.

[37]  M. McCall,et al.  Retinal transplants restore visually evoked responses in rats with photoreceptor degeneration. , 2001, Investigative ophthalmology & visual science.

[38]  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.

[39]  G. Fishman,et al.  Patterns of visual field progression in patients with retinitis pigmentosa. , 1998, Ophthalmology.

[40]  E. Berson Retinitis pigmentosa. The Friedenwald Lecture. , 1993, Investigative ophthalmology & visual science.

[41]  P. Gouras,et al.  The effects of bFGF on RCS rat eyes. , 1995, Current eye research.

[42]  T. Muramatsu,et al.  Functional Rescue of photoreceptors from the damaging effects of constant light by survival-promoting factors in the rat. , 1995, Investigative ophthalmology & visual science.

[43]  A. Bird,et al.  Repeated injections of a ciliary neurotrophic factor analogue leading to long-term photoreceptor survival in hereditary retinal degeneration. , 1999, Investigative ophthalmology & visual science.

[44]  L. A. Donoso,et al.  S-antigen in the developing retina and pineal gland: a monoclonal antibody study. , 1985, Investigative ophthalmology & visual science.

[45]  Richard L. Sidman,et al.  INHERITED RETINAL DYSTROPHY IN THE RAT , 1962, The Journal of cell biology.

[46]  E. Strettoi,et al.  Remodeling of second-order neurons in the retina of rd/rd mutant mice , 2003, Vision Research.

[47]  J. Ison,et al.  Intraretinal grafting restores visual function in light-blinded rats. , 1991, Neuroreport.

[48]  A. Laties,et al.  Activation of Caspase-3 in the Retina of Transgenic Rats with the Rhodopsin Mutation S334ter during Photoreceptor Degeneration , 1999, The Journal of Neuroscience.

[49]  R. Lund,et al.  Photoreceptor Layer Reconstruction in a Rodent Model of Retinal Degeneration , 1999, Experimental Neurology.

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

[51]  B. Ehinger,et al.  Graft-host connections in long-term full-thickness embryonic rabbit retinal transplants. , 1999, Investigative ophthalmology & visual science.

[52]  R. Lund,et al.  Long-term preservation of cortically dependent visual function in RCS rats by transplantation , 2002, Nature Neuroscience.

[53]  E. Strettoi,et al.  Modifications of retinal neurons in a mouse model of retinitis pigmentosa. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[54]  Yvette P Conley,et al.  The genetics of age-related macular degeneration. , 2003, Medsurg nursing : official journal of the Academy of Medical-Surgical Nurses.