May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
New Insights Into Photoreceptor Survival Due to Bmi1 Deletion
Author Affiliations & Notes
  • D. Zencak
    Unit of Gene Therapy & Stem Cell Biology, Jules Gonin Eye Hospital, Lausanne, Switzerland
  • S. V. Crippa
    Unit of Gene Therapy & Stem Cell Biology, Jules Gonin Eye Hospital, Lausanne, Switzerland
  • M. Jaquet
    Unit of Gene Therapy & Stem Cell Biology, Jules Gonin Eye Hospital, Lausanne, Switzerland
  • M. Tekaya
    Unit of Gene Therapy & Stem Cell Biology, Jules Gonin Eye Hospital, Lausanne, Switzerland
  • M. van Lohuizen
    Division of Molecular Genetics, Netherlands Cancer Institute, Amsterdam, The Netherlands
  • Y. Arsenijevic
    Unit of Gene Therapy & Stem Cell Biology, Jules Gonin Eye Hospital, Lausanne, Switzerland
  • Footnotes
    Commercial Relationships D. Zencak, None; S.V. Crippa, None; M. Jaquet, None; M. Tekaya, None; M. van Lohuizen, None; Y. Arsenijevic, None.
  • Footnotes
    Support Swiss National Science Foundation, ProVisu Foundation, Velux Foundation
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 4508. doi:
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      D. Zencak, S. V. Crippa, M. Jaquet, M. Tekaya, M. van Lohuizen, Y. Arsenijevic; New Insights Into Photoreceptor Survival Due to Bmi1 Deletion. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4508.

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

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Abstract

Purpose:: Rd1 mice are a well-known model of retinitis pigmentosa, characterized by a mutation in the Pde6b gene. They display a very rapid degeneration of rod photoreceptors (PRs) starting at 2 weeks of age, followed by a progressive loss of cones. We reported previously that Bmi1 loss in Rd1 mice prevents PR degeneration (Arsenijevic et al, ARVO 2005). Here, we provide a deeper characterization of this neuroprotection, focalizing on the time course and the appearance of several features of the disease.

Methods:: We compared the histology of Rd1 and Rd1-Bmi1-/- retinas on a FVB genetic background at several stages of retinal degeneration (P12, P15, and P30), and tested the ability of these mice to respond to light stimuli by electroretinogram (ERG) recording at different ages ranging from P16 to P35. FVB.129P2-Pde6b+mice served as sighted wild-type (WT) controls. Single Bmi1-/- on a C57/Bl6 background served as controls for the effect of Bmi1 loss in a healthy retina.

Results:: The number of PR rows in Rd1 mice was indistinguishable from Rd1-Bmi1-/- at P12. By contrast, at P15, Rd1-Bmi1-/- retinas harboured 8-10 rows of PRs compared to 2-4 rows in Rd1 mice. Similarly, at P30 Rd1-Bmi1-/- retinas contained 6-8 rows, while Rd1 mice presented a single scattered row of PRs. The rescued photoreceptors were positive for both recoverin and rhodopsin, and presented intact outer segments. Scotopic ERG recordings from Rd1-Bmi1-/- mice show a clear response to light stimuli, albeit not comparable to wild-type mice, while Rd1 mice typically presented flat ERG recordings. Other features of Rd1 mice include aberrant BrdU incorporation in the ONL at early stages of retinal degeneration and a faint CRALBP staining in Müller glia as the degeneration progresses. Rd1-Bmi1-/- mice harboured very rare BrdU+ cells in the ONL at P12 similarly to WT mice, as well as an intense wildtype-like CRALBP staining with clearly visible cell bodies and processes at both P15 and P30. Interestingly, on a C57/Bl6 background Bmi1-/- mice displayed a slight defect in bipolar, horizontal and amacrin cells at P30, with a consequently altered ERG response compared to wildtype WT littermates, but we did not observe any striking difference neither in the ONL nor in the CRALBP staining.

Conclusions:: Bmi1 loss efficiently prevented PR degeneration in Rd1 mice and preserved some functional PRs. It is so far unclear whether the mechanism underlying this survival is cell-intrinsic or rather related to Müller glia. Both hypotheses are currently being investigated.

Keywords: retinal degenerations: cell biology • neuroprotection • photoreceptors 
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