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Mario J Rojas, Tsung-Han Chou, Adam S Rosner, Rong Wen, Vittorio Porciatti; Injury-dependent retinal ganglion cell plasticity: effect of exogenous trophic factors. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2395.
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Distal injury of the retino-collicular pathway in mice causes reduction of retinal ganglion cell (RGC) electrical responsiveness associated with RGC shrinkage, BDNF overexpression, but not cell death (Yang et al, IOVS 2013). Here we investigated whether these adaptive changes are modifiable with exogenous trophic factors.
RGC function (pattern ERG, PERG), outer retina function (Photopic ERG, FERG) and inner/outer retina thickness (SD-OCT) were serially assessed in anesthetized C57BL/6J mice (n=24) before and 7, 14, 30, 60, 90 days after receiving surgical ablation of the superficial layers of the superior colliculus (SC). Two microliters of either BDNF (2µg/µl, n=10) or CNTF (1.5 µg/µl, n=10) were intravitreally injected in the left eye two weeks after right SC injury. Control mice (n=14) received SC injury but did not receive intravitreal injections.
In all mice groups, two weeks after SC injury the inner retina (ILM+NFL+RGCL+IPL) became significantly (P<0.01) thinner by 4.5 µm on average whereas the outer retina (INL+OPL+ONL+PRL) did not change. PERG amplitude dropped by 50% on average (P<0.01). Intravitreal injections of either BDNF or CNTF temporarily restored normal inner retina thickness for two weeks (P<0.01), which then returned to the post-injury thinned state. After either BDNF or CNTF injection, the PERG slowly recovered to reach a slightly subnormal plateau level between one month and three months (-25% of baseline on average, P=0.05). SC-injured controls that did not receive treatment displayed a slow recovery of PERG amplitude to a subnormal plateau as BDNF/CNTF-injected mice (two-way ANOVA: effect of treatment, N.S). For all the above conditions, the FERG was unchanged.
Early loss of RGC function after SC injury undergoes a spontaneous partial recovery while inner retina becomes thinner. Intravitreal injections of either BDNF or CNTF temporarily restore normal inner retina thickness but do not significantly alter spontaneous recovery of RGC function. These plastic changes are a conspicuous phenomenon that can be studied in an in vivo mouse model using translational tools such as OCT and PERG. Results have implications for better understanding, monitoring, and treatment of glaucoma and optic nerve disorders.
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