May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Effects of Photoreceptor Degeneration on Ganglion Cell Morphology and Survival
Author Affiliations & Notes
  • D. Damiani
    Institute of Neuroscience, CNR-Italian National Research Council, Pisa, Italy
  • F. Mazzoni
    Institute of Neuroscience, CNR-Italian National Research Council, Pisa, Italy
  • E. Strettoi
    Institute of Neuroscience, CNR-Italian National Research Council, Pisa, Italy
  • Footnotes
    Commercial Relationships  D. Damiani, None; F. Mazzoni, None; E. Strettoi, None.
  • Footnotes
    Support  NIH R01 12654, Italian CNR (ES)
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5181. doi:https://doi.org/
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    • Get Citation

      D. Damiani, F. Mazzoni, E. Strettoi; Effects of Photoreceptor Degeneration on Ganglion Cell Morphology and Survival. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5181. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Retinitis Pigmentosa (RP), a family of inherited diseases leading to photoreceptor death, is one of the major causes of blindness in the world. Among therapeutic strategies under study, the devise and implant of electronic prostheses has reached the stage of clinical trials. Retinal ganglion cells (RGCs) form the biological substrate that epiretinal prostheses stimulate to restore vision in RP; hence, the efficacy of such electronic implants depends upon RGCs viability.We studied the morphology and survival of RGCs in the rd1 mouse, an established model of autosomic recessive RP, at various stages from the onset of photoreceptor death.

Methods: : To study single RGCs, we generated a transgenic mouse, called rd1/Thy1-GFP, by crossing GFP-M mice, expressing GFP in a small population of RGCs of various types, with rd1 mice. As the two founder strains are on C57Bl and C3H backgrounds, respectively, repeated backcrossing was performed to isolate double mutants free of background effects. Genotypes were determined by PCR. We are presently studying the F7 generation. The transgenics display the typical rd1 phenotype, with rod death starting in the 2nd week of life. They also express GFP in a small number of heterogeneous RGCs.Retinal whole mounts from animals aged 1-7 months were stained with anti GFP antibodies and examined by confocal microscopy. After classification, each cell was studied quantitatively after Neurolucida tracings and Metamorph analysis. To estimate survival in the ganglion cell layer (GCL), retinal whole mounts were stained with ethidium and cell nuclei counted in serial optical sections.

Results: : The GCL in rd1 mutants aged 7 months displays clear signs of reorganization. Cell bodies are irregularly spaced, with empty areas suggestive of neuronal degeneration. Often cells appear arranged in circular domains resembling the initial stage of rosette formation. Individual RGCs labeled by GFP occur in lower number in rd1/Thy-1 GPF individuals as compared to the wild type founder; the morphology of these cells often reveals abnormally beaded dendrites. Pycnotic profiles are observed in the GCL.

Conclusions: : A similar study carried on in our laboratory on rd10 mutants revealed a remarkable preservation of RGCs morphology and survival up to 9 months. Observations on the GCL of rd1 mice, on the contrary, suggest faster and regressive remodeling of RGCs. Based on this and on previous studies on 2nd order neurons in this mutant, we conclude that the early and fast degeneration of photoreceptors, typical of the rd1 mutation, triggers profound remodeling and early deconstruction of all retinal layers.

Keywords: retinitis • ganglion cells • transgenics/knock-outs 
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