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Steven B. Koevary, Jennifer Nussey, Stephen Lake; Accumulation of Topically Applied Porcine Insulin in the Retina and Optic Nerve in Normal and Diabetic Rats. Invest. Ophthalmol. Vis. Sci. 2002;43(3):797-804.
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purpose. To explore the pharmacokinetics of topical insulin administration in
relation to retinal and optic nerve retention.
methods. Insulin eye drops (∼15 μL: 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/μg; P < 0.00001). Levels in diabetic retinas peaked at
60 minutes (0.66 pg/μg; 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/μg in normal rats at 20 minutes and 26 pg/μg 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.
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