June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Inducible retinal ganglion cell plasticity in DBA/2J mice
Author Affiliations & Notes
  • Tsung-Han Chou
    Bascom Palmer Eye Inst, Univ of Miami, Miller Sch of Med, Miami, Florida, United States
  • Ganeswara Rao Musada
    Bascom Palmer Eye Inst, Univ of Miami, Miller Sch of Med, Miami, Florida, United States
  • Giovanni Luca Romano
    Bascom Palmer Eye Inst, Univ of Miami, Miller Sch of Med, Miami, Florida, United States
  • Vittorio Porciatti
    Bascom Palmer Eye Inst, Univ of Miami, Miller Sch of Med, Miami, Florida, United States
  • Footnotes
    Commercial Relationships   Tsung-Han Chou, None; Ganeswara Musada, None; Giovanni Romano, None; Vittorio Porciatti, None
  • Footnotes
    Support  NIH RO1 EY019077, NIH P30-EY14801, Research to Prevent Blindness
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5855. doi:
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      Tsung-Han Chou, Ganeswara Rao Musada, Giovanni Luca Romano, Vittorio Porciatti; Inducible retinal ganglion cell plasticity in DBA/2J mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5855.

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

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Abstract

Purpose : Target-derived trophic support to RGCs can be chronically impaired by lesioning the superior colliculus, resulting in altered retinal protein expression and RGC function but not cell death (IOVS 2013, 54:1898-1904). Here we tested the hypothesis that molecular and functional plastic changes can be induced by temporarily blocking retrograde axon transport in the optic nerve.

Methods : DBA/2J mice in pre-glaucomatous stage (n=10) received repeated retrobulbar injections of 4% Lidocaine (4 µL, 40mg/mL, 4 injections every 3 days) in the left eye while the right eye received an equal volume of retrobulbar PBS. One month after treatment, RGC function was tested in each eye with PERG (Jorvec Corp.) at high (100%) and low (20% contrast) and also at high contrast with superimposed flicker at 11 Hz that induces functional hyperemia. Expression of relevant proteins (BDNF, TrkB, PSD95, Synaptophysin, GFAP) was assessed in a subgroup of mice (n=4), and RGC density was assessed in another subgroup of mice (n=6) from confocal images of flat mounted retina immunostained with RBPMS.

Results : Discriminant analysis revealed a dramatic difference (P<0.0001) between Lidocaine-treated and PBS-treated eyes in the level of expression of all proteins, with the exception of GFAP. Significant interocular differences (P<0.01) were also present when discriminant analysis was applied to protein subgroups representative of either neurotrophin expression (BDNF/TrkB) or synaptic structure/function expression (PSD95/Synaptophysin). While the standard PERG at 100% contrast was not different between Lidocaine-treated and PBS-treated eyes (P=0.6), the PERG at low contrast had a relatively larger amplitude (P=0.02) in the Lidocaine-treated eyes compared to PBS controls. Also, the PERG with superimposed flicker had a significant longer latency (P=0.04) in the Lidocaine-treated eyes compared to PBS controls. RGC density was similar (P=0.3) in treated and control eyes.

Conclusions : Temporary blockage of retrograde axon transport induces long-term changes of expression of key neurotrophic and synaptic markers that are associated with changes of RGC function such as contrast gain and adaptation to metabolic challenge. These results indicate that RGC plasticity can be induced in a mouse model relevant to glaucoma using a non-invasive, translational approach. It remains to be established whether Lidocaine-induced endogenous preconditioning is neuroprotective in glaucoma.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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