May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Blood Vessel and Glial Modifications in the Retina of the rd10 Mutant Mouse
Author Affiliations & Notes
  • E. Strettoi
    Istituto di Neuroscienze, CNR, Pisa, Italy
  • E. Novelli
    G.B. Bietti Foundation for Ophthalmology, Rome, Italy
  • Footnotes
    Commercial Relationships  E. Strettoi, None; E. Novelli, None.
  • Footnotes
    Support  NIH Grant EY12654, Italian CNR
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4890. doi:https://doi.org/
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      E. Strettoi, E. Novelli; Blood Vessel and Glial Modifications in the Retina of the rd10 Mutant Mouse. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4890. doi: https://doi.org/.

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

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Abstract

Purpose: : In human Retinitis Pigmentosa, (RP), retinal blood vessel attenuation accompanies and follows the degeneration of photoreceptors. Inner retinal cells, and particularly ganglion cells, depend upon retinal blood vessels for oxygen and trophic supply. Inner retinal cells constitute a biological platform of key importance for approaches aiming at restoring vision in RP individuals, especially when intervention strategies are based on the implant of electronic prostheses directly stimulating deep retinal neurons.Here we investigate the early and late effects of photoreceptor degeneration upon retinal blood vessels and glial network using the rd10 mutant mouse, a model of autosomal recessive RP with a mutation in the rod specific phosphodiesterase gene. Our ultimate goal is to assess the viability of inner retinal layers at various stages of the disease progression.

Methods: : Eyes of homozygous rd10 and wt control mice (aged 10 days to 9 months) were fixed in 4% paraformaldehyde, stained by immunofluorescence with antibodies against GFAP and counterstained with fluorescent Griffonia Simplicifolia to visualize retinal glial cells and blood vessels. After confocal microscopy examination, appropriate images of the inner, intermediate and superficial vessels were transferred to a Metamorph image analyser and processed to estimate vascular density and complexity.

Results: : Photoreceptor degeneration in rd10 mutant mice starts with rod progressive loss around P14 and peaks at P24. Already at these early stages, superficial and intermediate retinal vessels show a 16% decrement in complexity as compared to their wt counterpart. At P30, when rod degeneration is almost complete, vascular complexity does not show the expected increment associated to the completion of retinal development observed in the wt. An arrest in growth in the blood vessels of the mutant can explain this finding. Concomitantly, an increase in Muller cell reactivity for GFAP and hypertrophy of the astrocyte plexus are observed. The severity of the phenotype increases with time, ultimately resulting into a an overall loss of branches in blood vessels of all retinal plexa of the mutant and extensive reactive gliosis at 9 months.

Conclusions: : This study shows that even early stages of photoreceptor degeneration are accompanied by abnormal development and progressive atrophy of retinal blood vessels, possibly altering the viability of inner retinal cells. A widespread glial reactivity also occurs.

Keywords: retinitis • blood supply • glia 
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