April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
LKB1 Patterns Connections in the Retina in a SAD-A/B-Independent Manner
Author Affiliations & Notes
  • P. E. Voinescu
    Center for Brain Science, MCB, Harvard University, Cambridge, Massachusetts
  • B. N. Lilley
    Center for Brain Science, MCB, Harvard University, Cambridge, Massachusetts
  • Y. A. Pan
    Center for Brain Science, MCB, Harvard University, Cambridge, Massachusetts
  • J. R. Sanes
    Center for Brain Science, MCB, Harvard University, Cambridge, Massachusetts
  • Footnotes
    Commercial Relationships  P.E. Voinescu, None; B.N. Lilley, None; Y.A. Pan, None; J.R. Sanes, None.
  • Footnotes
    Support  NIH
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 4135. doi:
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      P. E. Voinescu, B. N. Lilley, Y. A. Pan, J. R. Sanes; LKB1 Patterns Connections in the Retina in a SAD-A/B-Independent Manner. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4135.

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

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Abstract

Purpose: : Our lab previously established the importance of LKB1 and SAD-A/B kinases working in concert for determining the polarity of cortical neurons. Here, we explored their role within retinal neurons, by analyzing the effect of their deletion on the structure and function of the retina.

Methods: : Using LKB1 and SAD-A/B conditional mutants crossed to retina specific Cre transgenic lines (Chx10-Cre, Pax6-Cre, Isl1-Cre, Rdps-Cre), we analyzed the effect of conditional allele deletion on retina morphology and visual function by immunohistochemistry/western blots, electron microscopy and electroretinography.

Results: : We show that LKB1-deficient retinas display striking morphological changes: horizontal and bipolar cells extend ectopic processes into the ONL, similar to those detected in retinae from Bassoon mutants, L-type calcium channel Cav1.4 nob2 mutants and normal aging animals. A distinct feature of LKB1-deficient retinas is that some amacrine subsets, in particular dopaminergic cells, also extend ectopic processes. At an ultrastructural level, we show that bipolar and horizontal cell processes are able to form ectopic synapses with rod terminals displaced in the ONL. ERG recordings indicate variable functional photoreceptor impairment.Unlike LKB1 knock outs, mutants deficient for SAD-A/B kinases display retinae that are normal morphologically and functionally. This result contrasts with studies in the cortex where developmental effects of LKB1 are mediated by SAD kinases.

Conclusions: : Our results indicate that LKB1 functions in a SAD-A/B-independent manner to pattern connections in the retina. To better understand the mechanisms triggering the phenotypic modifications we see in LKB1-deficient retina, we are currently investigating possible downstream players.

Keywords: retina: distal (photoreceptors, horizontal cells, bipolar cells) • retinal connections, networks, circuitry • synapse 
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