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Yuki Nakano, Aoi Ono, Mamoru Kobayashi, Yukari Takasago, Tohru Yamamoto, Kazuyuki Hirooka; Retinal ganglion cell loss in Alcadein α knockout mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3706.
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© ARVO (1962-2015); The Authors (2016-present)
Alcadein α (Alcα) is the major cargo of kinesin-1, which is subjected to anterograde transport in neuronal axons. We utilized mice in which Alcα has been knocked out and examined the long-term effect on retinal morphology and the effect on survival during postnatal development of retinal ganglion cells (RGC).
Experiments were performed using Alcα knock out mice (KO group) and wildtype mice (WI group). At 1.5, 3, 6, and 15 months after birth, histological examination was conducted to evaluate retinal damage by measuring the retinal thickness and the number of RGCs. Furthermore, the number of retrogradely labeled RGCs was also examined by using a flat mount retina. Intraocular pressure (IOP) measurements were made by using a Tonolab tonometer. Data were analyzed by an independent Student's t-test.
The number of retrogradely labeled RGCs was similar between the KO and WI group at 1.5 months after birth. However, the number of RGCs was significantly decreased at 3 (KO: 2280 ± 718 cells/mm2, WI: 3330 ± 684 cells/mm2; P < 0.01), 6 (KO: 2410 ± 280 cells/mm2, WI: 2990 ± 388 cells/mm2; P < 0.01), and 15 months (KO: 1960 ± 658 cells/mm2, WI: 2800 ± 454 cells/mm2; P < 0.01) after birth. Although the number of RGCs observed by histological examination was not significantly different between the KO and WI groups at 3 and 6 months after birth, the number of RGCs in the KO group was significantly decreased at 15 months after birth (KO: 98.5 ±13.8 cells/mm, WI: 119.3±18.2 cells/mm; P = 0.02). The thickness of each retinal layer was similar between the KO and WI group at each month after birth. No significant differences in the IOP levels were detected between KO and WI group at each month after birth.
We found that Alcα knock out mice showed spontaneously occurring RGC death without elevated IOP. We believe that these mice are models of normal-tension glaucoma (NTG) that offer a powerful system for investigating the mechanism of neurodegeneration in NTG and developing therapies directed at IOP-independent mechanisms of RGC loss.
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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