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SB Koevary, VW H Lam, G Patsiolopoulos; Accumulation of Porcine Insulin in the CSF and CNS Tissues Following Topical Application in Lewis Rats . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2325.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Our previous studies showed that topically applied insulin not only accumulated in the rat retina but in the optic nerve as well. This led us to speculate that topically applied insulin might also accumulate in the CSF and in CNS tissues that abut the ventricular and subarachnoid space. To investigate this, we quantified the levels of insulin in the CSF, LGN, brainstem, and cortex following topical insulin application. Methods: A single eye drop containing 0.75% porcine insulin + 0.5% Brij 78 was applied to fasted Lewis rats. Untreated littermates served as controls. CSF was extracted through the cisterna magna of anesthetized rats at various time points. The rats were then sacrificed and their LGNs, and a piece of their brainstem and prefrontal cortex were harvested, homogenized, centrifuged, and their supernatants assayed for insulin using an ELISA. Tissue pellets were assayed for protein; data were expressed as pg insulin/ug tissue. Results: CSF insulin levels were significantly elevated 10' after eye drop administration. Values (ng/ml; mean+SEM) were 0.24+0.09 and 0.67+0.15 for the baseline and 10 minute time points, respectively (p<0.03). Values fell by 30 minutes (0.16+0.1) but were again elevated at 45 minutes (0.51+0.1). Serum insulin levels rose at 10 minutes (0.62+0.09 vs. 0.2+0.07 for baseline, p<0.002) and remained elevated through 60 minutes. Porcine insulin levels in the right and left LGNs were significantly elevated 10 minutes after eye drop application. Values were: 0.03+0.008 and 0.12+0.02 for the left baseline and 10' time point, respectively (p<0.025), and 0.04+0.02 and 0.07+0.02 for the right baseline and 10' time point, respectively. The accumulation of insulin in the brainstem and cortex were also significantly elevated 10' after eye drop application. Values were: 0.04+0.02 and 0.22+0.05 for brainstem baseline and 10' values, respectively (p<0.01), and 0.08+0.03 and 0.19+0.03 for cortical baseline and 10' values, respectively (p<0.03). Conclusion: Our results showed that insulin accumulated not only in the LGN, but also in the brainstem and cortex, after topical application. These data suggest that optic nerve transport of insulin did not appreciably account for the presence of insulin in the LGN after topical application. CSF insulin levels showed bimodal peaks, with one occurring at 10' and one at 45'. While the second peak reflected the well-documented absorption of insulin from the blood, it is speculated that the first peak occurred as a result of absorption of insulin from tissues surrounding the nerve, that diffused there from the front of the eye.
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