July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
The ability of retinal ganglion cells to regenerate dendrites and synapses requires insulin signaling and is impaired by high fat diet intake
Author Affiliations & Notes
  • Jessica Agostinone
    Neurosciences, University of Montreal and CRCHUM, Montréal, Quebec, Canada
  • Luis Alarcon-Martinez
    Neurosciences, University of Montreal and CRCHUM, Montréal, Quebec, Canada
  • Heberto Quintero
    Neurosciences, University of Montreal and CRCHUM, Montréal, Quebec, Canada
  • Sara Vucetic
    Neurosciences, University of Montreal and CRCHUM, Montréal, Quebec, Canada
  • Nicolas A Belforte
    Neurosciences, University of Montreal and CRCHUM, Montréal, Quebec, Canada
  • Adriana Di Polo
    Neurosciences, University of Montreal and CRCHUM, Montréal, Quebec, Canada
  • Footnotes
    Commercial Relationships   Jessica Agostinone, None; Luis Alarcon-Martinez, None; Heberto Quintero, None; Sara Vucetic, None; Nicolas Belforte, None; Adriana Di Polo, None
  • Footnotes
    Support  The Glaucoma Research Foundation (San Francisco, CA), and the Canadian Institutes of Health Research
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2613. doi:
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      Jessica Agostinone, Luis Alarcon-Martinez, Heberto Quintero, Sara Vucetic, Nicolas A Belforte, Adriana Di Polo; The ability of retinal ganglion cells to regenerate dendrites and synapses requires insulin signaling and is impaired by high fat diet intake. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2613.

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

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Abstract

Purpose : The retraction of retinal ganglion cell (RGC) dendrites and synapse loss are proposed to be an early pathological alteration in glaucoma. Aberrant insulin signaling has been associated with neurodegenerative diseases characterized by dendritic pathology, however, its role in the response of vulnerable neurons is poorly understood. We investigated the effect of insulin on dendrite and synapse regeneration and asked whether insulin resistance alters the regenerative ability of RGC

Methods : Transgenic mice expressing YFP protein in RGC were subjected to optic nerve axotomy or microbead-induced ocular hypertension (OHT). Insulin was administered daily (i.p. or drops) starting when RGC dendrites had already retracted, dendritic trees and synapses were analyzed 4 to 7days later. Excitatory post-synaptic sites were visualized after biolistic transfection of a CMV:PSD95-YFP plasmid. RGC survival was assessed by quantification of RBPMS-positive cells and their light response measured by photopic negative response (PhNR) recordings. A group received a high fat diet to induce pre-diabetic insulin resistance

Results : Insulin, independently of delivery route, promoted robust RGC dendrite regeneration, restoring process length, arbor area and complexity after axotomy or OHT. Quantitative analysis of dendritic parameters demonstrated a 36% increase in process length and 43% larger arbor area with insulin relative to vehicle-treated neurons (Vehicle: length= 2961 ± 180 µm, area= 77 ± 6 x 103 µm2, Insulin: length= 4677 ± 136 µm, area= 142 ± 7 103 µm2; N= 5-6 mice/group, n= 40-50 RGCs/group). Insulin restored excitatory postsynaptic sites on RGC dendrites independently of subtype, increasing PSD95 puncta density by 76%, 93%, and 93% in ON-S, OFF-S, and OFF-T RGCs, respectively (N=5-6/group). Insulin rescued the PhNR amplitude and promoted robust RGC neuroprotection. High fat diet intake, leading to insulin resistance, blocked the ability of insulin to promote RGC dendrite regeneration and survival

Conclusions : Our study identifies insulin as a critical factor for RGC dendrite regeneration and functional recovery, while high fat diet leading to insulin resistance impaired this pro-regenerative response. A better understanding of RGC insulin signaling in glaucoma, including pre- and diabetic conditions, might have implications to prevent synaptic loss and visual deficits

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

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