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alice brandli, Sharon Spana, Jonathan Stone, Retinal and Cerebral Neurobiology; Remote ischemia: effects on retinal function and neuroprotection in a light damage model. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3259. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Remote ischemic pre-conditioning (RIP) has found to be protective of heart and brain against ischemic injury. We have tested the effects of RIP on retinal function, and whether RIP is protective to the retina.
To generate ischemia remote from the retina, one hind limb was made ischemic with a pressure cuff applied for up to 10 min. A temperature probe on the footpad confirmed blockage of the circulation. To test the impact of RIP on retinal function we recorded the dark-adapted flash electroretinogram (ERG) in Sprague-Dawley rat at baseline (n=5 group), and 10 mins after RIP (2x5 minutes: 5 minutes cuff on, 5 minutes off, 5 minutes on ) or sham RIP treatment . To test the neuroprotective potential of RIP, RIP (2 x 5 mins) was delivered immediately before exposure of the animal to damaging light (1000 lux, 24 hours, >12 hours dark adaption). 7 days later, the ERG was recorded and structural status of the retina were assess in 4 experimental groups (RIP-conditioned and light exposed, and three control groups -light damaged, RIP-exposed and untreated controls, n =6 per group). ERGs were analysed for the a- and b-waves, and expressed as percentage change (mean ± SEM).
In the normal retina RIP increased the amplitude of a-(25% ± 3 vs -2% ± 1, P < 0.01, n = 5) and b-waves(27% ± 2 vs. 1.0% ± 1, P < 0.01). In the test of neuroprotection, RIP preserved photoreceptor and bipolar function against light damage (a-wave: 27% ± 3 vs. 7.0% ± 5, P < 0.01, n = 6) and (b-wave: 25% ± 4 vs. 3% ± 5, P < 0.01, n = 6). Muller cell upregulation of a stress-inducible protein was reduced (0.4 ± 0.09 vs. 0.5 ± 0.04 p< 0.0001, n = 6 ), the outer nuclear layer was thicker (0.3 ± 0.01 vs. 0.3 ± 0.0 p< 0.0001, n =6) and the number of cells undergoing apoptosis was less (250 ± 6 vs. 214 ± 6 p< 0.0001, n =6) in the RIP treated light exposed animals.
The effect of RIP on retinal function is a novel finding. Remote ischemic has marked neuroprotective effects in the retina, and may offer a non-invasive therapeutic treatment to prevent or mitigate photoreceptor degeneration of the retina.
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