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Steven Roth, John C Dreixler, Biji Mathew; Media from Hypoxic-Preconditioned Bone Marrow Stem Cells Rescues Ischemic Retina. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2706.
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© ARVO (1962-2015); The Authors (2016-present)
Hypoxic preconditioning attenuated damage from retinal ischemia in rats. We have shown that post-ischemic conditioning by a brief ischemic stimulus 24 h after ischemia is also ameliorative. Studies have suggested that bone marrow stem cells (BMSCs) could abrogate ischemic injury. We hypothesized that administration of media from hypoxic preconditioned autologous BMSCs would provide "direct delivery" of neuroprotection and rescue from retinal ischemia even when adminstered 24 h after ischemia.
Retinal ischemia was produced in adult Wistar rats by increasing intraocular pressure to 130-135 mm Hg for 55 min. BMSCs were exposed to 1% O2 for 72 h (HCM); control group was normoxic cells (nCM), and another control was media exposed to hypoxia for the same exposure time (uHCM). Media from HCM, nCM, or uHCM (media without cells that was exposed to hypoxia), was injected into the vitreous 24 h after ischemia. Recovery was assessed after 7 d using electroretinography 10 micron thick paraffin-embedded retinal sections for histology; TUNEL was examined as well. Cytokine arrays examined protein levels in the cell media under hypoxic and the two control conditions.
Intravitreal injection of HCM media 24 h after ischemia significantly improved retinal function (Fig 1), decreased retinal cell loss, and attenuated apoptosis vs the two controls. 22 cytokines were significantly increased in media from hypoxic vs normoxic BMSCs; largest (> 200% and P < 0.001 vs normoxic) were Prolactin R, IL1 R6, CINC2a, Leptin, IL1a, L-selectin, IL10, IL6, IL4, and IL2.
Hypoxic preconditioned BMSC media robustly restored retinal function and prevented cell loss after ischemia. Possible candidate proteins were identified that include pro- and anti-inflammatory cytokines; exact functions in this remarkable post ischemic rescue remain to be determined.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
The injection of media from hypoxic preconditioned BMSCs significantly enhanced recovery of ERG b wave, P2, and OP compared to normoxic BMSCs media and to unconditioned hypoxic media (containing no cells). A-D shows comparison of hypoxic media to normoxic media, and E-H shows comparison of hypoxic BMSCs media to unconditioned hypoxic media. In all cases, solid line is hypoxic BMSCs media; dotted line in A-D is normoxic BMSCs media and in E-H is unconditioned hypoxic media (no cells). # indicates P < 0.005 between groups.
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