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H. E. Beggs, C. Bouquet, G. Lambright, H. Yang, G. Nielsen, D. Yasumura, M. T. Matthes, J. L. Duncan, M. M. LaVail; Control of Müller Glial Cell Morphology by Focal Adhesion Kinase Impacts Visual Function in Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1901.
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© ARVO (1962-2015); The Authors (2016-present)
Focal adhesion kinase (FAK) is an important signaling node that has been shown to play a crucial role in nervous system development as well as in orchestrating neuronal and glial cell morphology. However, its role in retinal function in vivo and its subsequent impact on visual processing has not been studied.
Retinal-specific deletion of FAK was accomplished by crossing the FAK-flox line to mice expressing Cre recombinase under control of the Six3 promoter. Retinal function was analyzed by electroretinography (ERG) and optomotry. Individual fills of Müller glial cells were accomplished by subretinal injection of adenoviruses containing eGFP and Cre in a FAK-floxed background, and 3D reconstruction was performed with Imaris software. Measurements of light transmission were performed in retinal explants with a Zeiss Pascal microscope.
FAK deletion in the retina (but not the RPE or lens) resulted in animals with impaired retinal function as measured by ERG. Specifically, these animals displayed a 40% reduction of the scotopic (dark adapted) a- and b-wave response amplitudes, and a significantly decreased optokinetic behavioral reflex. Surprisingly however, histological analysis did not reveal any gross morphological abnormalities, and photoreceptor sensitivity was shown to be normal, thus offering no explanation for the functional deficits observed. Upon closer examination, we found a unique defect in the shape of Müller glial cell endfoot processes, with the FAK mutant displaying a more simplified vitreal segment and a subsequent 2-fold reduction in surface area. Since Müller glia have been shown to act as optical fibers, with their funnel-shaped endfeet serving as light collectors (Franze et al, 2007, PNAS), we examined whether this morphological change could account for the ERG defects in FAK mutants. Remarkably, we found that the FAK mutant retinas transferred 2.2 times less light to the photoreceptors than controls, and this decrease correlated with the changes in ERG response amplitudes.
This study demonstrates an unexpected function for FAK in controlling Müller glial endfoot morphology. Importantly, we have shown that this morphological change corresponds to decreased light transmission in the retina, which highlights the importance of Müller glia as light guiding elements in the optical path.
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