PURPOSE. Our earlier findings showed that insulin, applied topically, accumulated not only in the retina, but also the optic nerve. These data supported the notion that, by virtue of the optic nerve’s association with the meninges, topical insulin might similarly accumulate in the CSF. To investigate this possibility, we quantified the levels of insulin in the CSF obtained from the cisterna magna at various time points following insulin eye drop administration in rats. METHOD. An eye drop (0.75% porcine insulin + 0.5% Brij 78) was applied to the left eye of fasted Lewis rats. CSF was extracted through the cisterna magna from anesthetized rats 10, 30, and 45 minutes later. Rats were then sacrificed and their serum harvested. Untreated rats served as baseline controls. CSF and serum insulin was quantified using an ELISA kit.
RESULTS. CSF insulin levels were significantly elevated 10 minutes after eye drop administration, compared to baseline (reflecting negligible cross-reactivity to rat insulin). Values (ng/ml; means+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 compared to 0.2+0.07 for baseline, p<0.002) and remained elevated through 45 minutes.
CONCLUSIONS. Our results showed that, following topical application, insulin peaked in the CSF after 10 minutes, fellback to baseline at 30 minutes, and then peaked again at 45 minutes. It is well established that there is about a 45 to 60 minute delay in the uptake of hormones such as insulin following serum elevations. Thus, it is likely that the second peak reflects the absorption of insulin from the blood (this insulin having gotten into the blood by absorption through the lacrimal and/or conjunctival blood vessels). It is speculated that the first peak occurs as a result of the direct absorption of insulin from surrounding tissues, into the CSF encircling the optic nerve.