July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Degenerating retinal ganglion cells disconnect from bipolar cells using diverse strategies
Author Affiliations & Notes
  • Luca Della Santina
    Ophthalmology, University of California San Francisco, San Francisco, California, United States
  • Alfred Yu
    Ophthalmology, University of California San Francisco, San Francisco, California, United States
  • Alan Tran
    Ophthalmology, University of California San Francisco, San Francisco, California, United States
  • Kelly Mai
    Ophthalmology, University of California San Francisco, San Francisco, California, United States
  • Yvonne Ou
    Ophthalmology, University of California San Francisco, San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Luca Della Santina, None; Alfred Yu, None; Alan Tran, None; Kelly Mai, None; Yvonne Ou, None
  • Footnotes
    Support  BrightFocus Foundation, E. Matilda Ziegler Foundation for the Blind, RPB Unrestricted Grant to UCSF, NIH-NEI EY002162 Core Grant for Vision Research
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2010. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Luca Della Santina, Alfred Yu, Alan Tran, Kelly Mai, Yvonne Ou; Degenerating retinal ganglion cells disconnect from bipolar cells using diverse strategies. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2010.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Retinal ganglion cells (RGCs) undergo progressive loss of their glutamatergic excitatory postsynaptic sites when intraocular pressure (IOP) is elevated in animal models of experimental glaucoma (Della Santina et al. JNeurosci 2013, Ou et al. JNeurosci 2016). It is currently unknown whether this process follows a common pattern across all RGCs or multiple disconnection strategies are employed by different RGC types. To this purpose we investigated the connectivity between individual RGCs and presynaptic bipolar cells (BCs) after acute IOP elevation.

Methods : IOP was elevated unilaterally by laser photocoagulation of the limbal and episcleral veins of adult CD-1 mouse eyes, generating transient IOP elevation lasting one week. Whole-mount retinas were isolated and biolistically transfected to label RGCs and their excitatory postsynaptic sites (PSD95). Immunostaining with CtBP2 labeled presynaptic ribbons while immunostaining with Synaptotagmin-2 labeled axon terminals of Type-2 and Type-6 bipolar cells. RGC connectivity was measured by colocalization analysis in three dimensions on confocal imaging stacks of individual RGC dendrites at 7, 14, and 30 days after IOP elevation. Alpha RGC types (ON-Sustained, αON-S; OFF sustained, αOFF-S; OFF transient, αOFF-T) were investigated in this study.

Results : Colocalization between ribbons and PSD95 was significantly lower than control as early as 7 days after IOP elevation (Control vs Laser, αON-S: 90±2% vs 62±4% p=0.001, αOFF-S: 74±3% vs 48±3% p=0.0007, αOFF-T: 78±3% vs 55±4% p=0.002). αON-S and αOFF-S RGCs establish preferential connectivity with type-6 and type-2 bipolars in control conditions, respectively. This preferential connectivity is lost as early as 7 days after IOP elevation for sustained alpha RGC types (Control vs Laser; αON-S: 64±2% vs 37±4% p=0.001; αOFF-S: 68±2% vs 38±4% p=0.003), while αOFF-T RGCs only undergo a slight reduction of their connectivity to type-2 bipolars (Control vs Laser: 38±3% vs 23±5% p=0.052).

Conclusions : Alterations to synaptic connectivity at the BC-RGC synapse are among the earliest pathologic events affecting the inner retina in mouse models of experimental glaucoma. At this synapse, ribbons are disassembled before PSD95 across all RGCs examined, indicating that presynaptic component is also affected at early disease stages. The specificity of this disconnection pattern is specific to the individual RGC type.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×