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Vittorio Porciatti, Mario Joseph Rojas, Tsung-Han Chou, Rong Wen; Dynamics of retinal ganglion cell plasticity induced by deficiency of target-derived factors in the mouse. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3607.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate molecular changes associated with functional and structural changes of retinal ganglion cells (RGCs) after lesion of the superior colliculus (SC).
Twenty-four C57BL/6J mice were tested with PERG (to assess RGC function) and OCT (to measure inner retina thickness) before and after (10, 30, 60, 90,250 days) unilateral lesion of the SC. At designated dates, retinas in each group were harvested for confocal images of TUJ1-labeled RGCs (to evaluate RGC density) and densitometry of western blots to evaluate expression of BDNF, TrkB, PSD95, Synaptophysin, and GFAP.
After SC lesion there was a marked early PERG loss (-65% within 10 days) followed by a slow (within 30 days) recovery to a subnormal plateau (-25% of baseline) lasting the entire observation period. Inner retina thickness (NFL+RGCL+IPL) became progressively thinner by 6 µm within 30 days and remained stable thereafter. The temporal profile of PSD95 expression mirrored that of inner retina thickness, with a progressive decrease of expression up to 50% that remained stable thereafter. All other molecular profiles displayed a transient (within 30 days) overexpression by about 20% followed by a negative rebound and stabilization to values close to that of controls, with the exception of BDNF that increased overexpression to about 1.8 times that of control values by 8 months. RGC density was unaffected by SC lesion.
Deficiency of target-derived trophic factors is a common cause of neurological diseases.Lesion of the main source of trophic support (SC) in the mouse induces adaptive changes in the inner retina resulting in altered structure and function of RGCs but not cell death. The PERG undergoes a tri-phasic change while inner retina becomes progressively shrunk together with reduced expression of PSD95, a structural synaptic marker. The transient increase of overexpression of endogenous BDNF, TrkB and synaptophysin as well as the long-lasting increase of endogenous BDNF expression suggest compensatory mechanisms to sustain electrical activity of RGCs. The transient increase of GFAP suggests modest astrocytic activation. A sizeable time window of RGC plasticity qualitatively similar to that described here is likely to occur in early stages of glaucoma and other optic neuropathies, and be amenable to treatment to rescue RGCs from death and spare their function.
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