Accumulation of topically applied porcine insulin in the retina and optic nerve in normal and diabetic rats.
OBJECTIVE
To explore the pharmacokinetics of topical insulin administration in relation to retinal and optic nerve retention.


METHODS
Insulin eye drops (approximately 15 microL: 0.75% porcine insulin + 0.5% permeation enhancer) were applied to the eyes of normal and diabetic rats. The rats were killed at various intervals up to 16 hours, and the retinas and optic nerves from both eyes were analyzed for the presence of insulin in an ELISA. The extent to which systemically absorbed insulin accounted for the findings of insulin in the retina was explored by examining the effects of intravenously injected insulin on retinal insulin levels and by examining the effects of eye drop administration in decapitated rats.


RESULTS
Insulin levels rose significantly and peaked in the retina of normal rats 20 minutes after eye drop application (0.7 pg/microg; P < 0.00001). Levels in diabetic retinas peaked at 60 minutes (0.66 pg/microg; P < 0.004) and remained elevated for a longer period than in normal rats. The contralateral retina showed delayed accumulation of lesser amounts of insulin in both normal and diabetic rats. Significant elevations also occurred in the optic nerves in normal and diabetic rats, with concentrations reaching 13 pg/microg in normal rats at 20 minutes and 26 pg/microg in diabetic rats at 5 hours. Topical insulin application resulted in a decrease in serum glucose concomitant with an increase in serum porcine insulin. It did not appear, however, that the systemic absorption of insulin contributed to the accumulation of insulin in the ipsilateral retinas, for two reasons: The intravenous injection of a high concentration of insulin did not appreciably influence retinal insulin levels, and the application of insulin eye drops to decapitated rats still resulted in the accumulation of insulin in the retina.


CONCLUSIONS
These results led to the conclusion that topically applied insulin accumulates in the retina and optic nerve in normal and diabetic rats, with levels remaining elevated longer in diabetic animals. It did not appear that systemically absorbed insulin, resulting from ocular drainage, contributed to this effect.
Koevary
Steven B
SB
Ocular Research Center, New England College of Optometry, 424 Beacon Street, Boston, MA 02115, USA. koevarys@ne-optometry.edu
Nussey
Jennifer
J
Lake
Stephen
S
D000042:Absorption; D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D007328:Insulin / Q000493:pharmacokinetics*; D009883:Ophthalmic Solutions / Q000493:pharmacokinetics; D009900:Optic Nerve / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000378:metabolism*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D009883:Ophthalmic Solutions