Abstract
Purpose:
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor first identified from the conditional medium of a rat type-1 astrocyte cell line, the ventral mesencephalic cell line 1 (VMCL1). We have shown previously that recombinant human MANF protects photoreceptors in a retinal degeneration rat model carrying the S334ter rhodopsin mutation. In the present work, we examined the effect of MANF on the electrophysiolocal activities of retinal cells in the rd10 mice, a retinal degeneration model carrying the Pde6brd10 mutation.
Methods:
The rd10 mice were kept at ~50 lx 12:12 light:dark cycle. Recombinant human MANF was expressed in E. coli and purified. At PD18 (postnatal day 18), MANF (2 µg in 1 µl) was intravitreally injected to the right eyes of rd10 mice, and the left eyes were injected with PBS (phosphate buffered saline) as controls. Scotopic ERG responses were recorded 10 days later using an LKC UTAS system. Dark-adapted animals were anesthetized with a mixture of ketamin and xylazine. ERGs were elicited by white light flashes of -0.4 log cd-s/m2. The b-wave amplitudes of the treated eyes were compared with those of the control eyes. Statistical significance between the two groups was determined by Student t test.
Results:
The a-wave was undetectable at -0.4 log cd-s/m2 in the rd10 mice at PD28. In the control eye injected with PBS, the b-wave amplitude was 82.4±10.7 μV (mean±SD, n=5). The b-wave in the treated eye was 115±16.5 μV (n=5, P=0.0017), significantly higher than the control.
Conclusions:
Intravitreal injection of recombinant human MANF significantly preserves b-wave in the rd10 mice. Our results thus demonstrate that MANF not only preserves photoreceptor cells, but also their light-sensing function.