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Zhao Hongwei, Hironori Uehara, Ling Luo, Chuang Nie, Alex Jones, Balamurali Ambati, Xiaohui Zhang, Hu Lianna, Qiu Changyu; Membrane bound Flt-1 protects against optic nerve degeneration in nerve crush injury in rats. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5737. doi: https://doi.org/.
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In recent years, VEGF-B has been shown to be a potent neuroprotective factor and an apoptosis inhibitor, rather than an angiogenic factor.VEGF-B deficiency exacerbated retinal ganglion cell death.VEGF-B increased the number of surviving retinal ganglion cells via its receptor (Flt-1) in rat optic nerve injury.Flt-1 has two isoforms: membrane-bound form (mFlt-1) and soluble form(sFlt-1). Recently, we demonstrated that sFlt-1, as an anti-angiogenic factor, strongly protect photoreceptor avascularity. In this study, we explored whether either the soluble or membrane isoform of Flt-1 could protect against optic nerve degeneration.
To establish a rat model of optic nerve damage,adult female 200-250g Spraque-Dawley rats was exposed through a supraorbital approach and crushed bilaterally within the orbit, 2 mm from the eye, using forceps as described previously.Retinal ganglion cells (RGC), inner/outer nuclear cells degeneration was determined by TUNEL staining and immunohistochemistry. The levels of sFlt-1 and mFlt-1 were detected by RT-PCR and Western Blot at 6 hr, 24hr, 3 day, 7 day, and 21 day after injury. Intravitreal injection with mFlt-1 or sFlt-1 plasmid was performed at 24 hr after injury. RGC and inner/outer nuclear cells apoptosis and degeneration evaluation was repeated at day 21 after intervention.
The level of mFlt increased dramatically at 6 hr after injury, peaked at 48th hour, gradually reduced after a week. Comparably, the level of sFlt-1 barely changed at each time point. RGC and inner/outer nuclear cells apoptosis and degeneration were much lower in mFlt-1 treatment group than that of sFlt-1treatment group.
mFlt-1, but not soluble was able to promote RGC preservation after optic nerve injury.
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