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Yuta Kitamura, Toshiyuki Oshitari, Guzel Bikbova, Takayuki Baba, Shuichi Yamamoto; Neuroprotective effects of topical neurotrophic factors applied individually or in combination on retinal ganglion cells of rats after optic nerve crush. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2487.
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© ARVO (1962-2015); The Authors (2016-present)
To assess the neuroprotective effects of three neurotrophic factors administered topically on retinal ganglion cells (RGCs) of rats following optic nerve crush.
Thirty-six Sprague-Dawley rats were divided into 6 groups with 6 rats/group. Rats were treated with topical 100 mM TUDCA, 100 mM citicoline, 10 ng/ml NT-4, combined TUDCA-citicoline (Doublet), or combined TUDCA-citicoline-NT-4 (Triplet). After 2 weeks, the number of surviving RGCs was determined by Brn3a immunostaining of retinal flat mounts. The adverse events after the topical administration were also recorded.
Without any treatment, the density of RGCs was 4.64±7.31/mm2 at 2 weeks after the optic nerve crush which was significantly fewer than the 1857±334.7/mm2 in the normal control retinas (P <0.0001). The density of RGCs in the TUDCA-treated eyes was 678.4±144.6/mm2, in citicoline-treated eyes was 701.1±356.7/mm2, in NT-4-treated eyes was 70.4±29.8/mm2, in Doublet-treated eyes was 790±434.6/mm2, and in the Triplet-treated eyes was 795±563.6/mm2. The density of RGCs in all of the eyes that had received the different neurotropic agents was significantly higher than that of RGCs without treatment (P <0.0001). While the density of the RGCs in NT-4 treated eyes was lower than in the other treated groups, the density of RGCs among the other groups was not significantly different. The only adverse event was neovascularizations of the cornea, iris, and dilatation of the choroid vessels in 8 of 13 rats (62%) in the Doublet treated eyes.
Optic nerve crush causes a loss of RGCs and topical application of three neurotrophic factors individually or in combination protected the RGCs from death. Although the combination of neuroprotective agents has been shown to be effective in vivo, we should be aware of complications such as neovascularizations can occur in vivo. Further studies to identify the cause of adverse effects need to be performed.
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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