PURPOSE. Our previous pharmacokinetic studies showed that the topical application of porcine insulin led to its retention in the retina. These earlier studies were undertaken to investigate the feasibility of readily targeting drug therapy to the retina in diabetes. Our more recent data demonstrated that the optic nerve and CSF also accumulated insulin after topical application. These latter findings led to the speculation that topically applied drugs might be readily transported, actively or passively, into the central nervous system, in particular, the lateral geniculate nucleus (LGN). The purpose of this study was to begin to investigate this possibility. METHOD. A single eye drop (0.75% porcine insulin + 0.5% Brij 78) was applied to the left eye of 2 month old, fasted, normal Lewis rats. The rats were sacrificed 10 and 30 minutes later, and their sera harvested. Their left and right LGNs were removed, homogenized in buffer, centrifuged, and the supernatants assayed for insulin using a porcine insulin ELISA kit (Alpco). The tissue pellets were assayed for protein. Data were expressed as pg/ug protein.
RESULTS. : Porcine insulin levels in the right and left LGNs were significantly elevated 10 minutes after eye drop application. Values (means+SEM) were as follows: 0.017+0.003 and 0.015+0.005 for baseline left and right LGNs, respectively (baseline values reflected the negligible cross reactivity of rat insulin in this assay), and 0.08+0.02 and 0.06+0.02 for 10 minute left and right LGNs, respectively (p<0.02 for each 10 minute value versus baseline). Thirty minute levels were similar to baseline. Serum insulin levels were elevated at both 10 and 30 minutes.
CONCLUSIONS. These data demonstrated that topically applied insulin can accumulate in the LGN. Our previous data showing a negligible increase in serum insulin levels 10 minutes after eye drop administration suggest that this increase is not due to systemic uptake of insulin that was absorbed through the lacrimal system. This is further supported by the low levels of insulin in the LGNs at 30 minutes, even while serum insulin levels were elevated.