Roles of PI3K and JAK pathways in viability of retinal ganglion cells after acute elevation of intraocular pressure in rats with different autoimmune backgrounds |
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Authors: | Yao Huang Zhiwei Li Ningli Wang Nico van Rooijen Qi Cui |
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Institution: | (1) Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, P.R. China;(2) Department of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Sciences, Beijing, P.R. China;(3) Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, 1081 BT Amsterdam, The Netherlands |
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Abstract: | Background We recently showed that whereas inhibition of PI3K/akt or JAK/STAT pathway promoted retinal ganglion cell (RGC) survival after
optic nerve (ON) injury in Fischer 344 (F344) rats, the same inhibition resulted in aggravated RGC loss after acute intraocular
pressure (IOP) elevation in Sprague Dawley (SPD) rats. In addition, the responses of macrophages to ON injury and acute IOP
elevation were different between F344 and Lewis rats, i.e., different autoimmune profiles. Using an acute IOP elevation paradigm
in this study, we investigated 1) whether autoimmune background influences PI3K/akt and JAK/STAT functions by examining the
effect of PI3K/akt and JAK/STAT pathway inhibition on RGC survival in F344 and Lewis rats, and 2) whether differential actions
of macrophages occur in PI3K/akt and JAK/STAT pathways-dependent modulation of RGC survival. IOP elevation was performed at
110 mmHg for 2 hours. PI3K/akt and JAK/STAT pathway inhibitors were applied intravitreally to block their respective pathway
signaling transduction. Because macrophage invasion was seen in the eye after the pathway inhibition, to examine the role
of these pathways independent of macrophages, macrophages in the retina were removed by intravitreal application of clodronate
liposomes. Viable RGCs were retrogradely labelled by FluoroGold 40 hours before animal sacrifice. |
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Keywords: | |
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