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Pearl S. Rosenbaum, Daniel Lax, Nitin Goyal, Aleksandr Melamud, Jie Li, Jin Zhou, Frank C. Barone, Daniel M. Rosenbaum; Thrombopoietin Plus Hypothermia Provide Additive Improvement Of Function Following Rat Retinal Ischemia. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2655.
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Recently, we showed Thrombopoietin (TPO) protection of brain from ischemic stroke (J Cereb Blood Flow Metab. 2010; Sep 29). Hypothermia (HYPO) provides significant CNS protection (Neurosci Biobehav Rev. 21(1): 31-44, 1997) and needs investigation in combination with neuroprotective drugs. Here TPO or ocular HYPO alone or combined was compared to control conditions (e.g., PBS for TPO; normal temperature; NORM, for HYPO) to support our previous data and establish feasibility for combined intervention.
Retinal ischemia was produced in male Sprague Dawley rats. High intraocular pressure (120 mmHg) induced right eye retinal ischemia for 45 minutes. Electroretinograms (ERG) α- and β-waves were measured in each eye before ischemia and 7 days later. TPO (0.03-3.0 µg/kg, i.v.) was compared to PBS administered immediately after ischemia. HYPO (i.e., 32oC or 30oC) was compared to NORM (i.e., 34oC) ocular temperature applied during ischemia. Retinal function (measured as percent normal eye ERG baseline) was calculated as post-wave ratio (post-ischemia eye/post-normal eye) to pre-wave ratio (pre-ischemia eye/pre-normal eye).
Following retinal ischemia, the ERG α-wave did not differ but ERG β-wave decreased. TPO administration protected retinal function (PBS=14+3%; 0.03µg/kg=32+10%; 0.1µg/kg =33+2%; 0.3µg/kg=38+6%; N=8-15; all TPO doses differed from PBS, p<0.05; 0.1 µg/kg TPO was selected for combination work). HYPO produced protection of retinal function (NORM=23+3%; 32oC=52+4%; 30oC=87+6%; N=6-15; 32oC differed from other groups, p<0.001, and was selected for combination work). Combination work demonstrated additive effects (NORM+PBS=24+3%; NORM+TPO=37+3%; HYPO+PBS=51+4%; HYPO+TPO=77+11%; N=3-18; all groups different from each other, p<0.01).
TPO plus HYPO provide additive protection of retinal function following ischemia.
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