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C. Robinson, P.R. Mayo, II, J. Lee, S.B. Koevary; The Topical Application of Glial–Derived Neurotrophic Factor (GDNF)–Containing Eye Drops in Rats Results in its Accumulation in the Retina and Cerebrospinal Fluid (CSF) . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5092.
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We previously reported that topically applied peptides accumulated in the posterior segment of the eye, and CNS. In this study, we determined whether the topical application of GDNF, a fairly large peptide (∼30kD), could similarly accumulate in the retina and CSF. GDNF has been reported to have neuroprotective effects in the brain and retina.
A single eye drop containing 1 microgram/ml of GDNF and 0.5% Brij 78 (a permeation enhancer) was applied to the right eye of 2–3 month old Lewis female rats. The rats were then sacrificed at regular intervals and their retina, CSF, and serum were harvested. The retinas were homogenized and their supernatants, as well as the CSF and serum samples, were analyzed for the presence of GDNF using an ELISA Development System (R&D Systems). Values are expressed as the mean ± SE.
Retinal GDNF levels rose significantly 10 and 20 minutes after application (72±9.5 and 72+10 pg/microgram) compared to controls (42±4, n = 5/gp; p< 0.05). Similarly, eye drop–treated rats showed significantly elevated CSF levels of GDNF after 10 minutes (100±23) compared to controls (36.4±8.6)(n =14 and 15, respectively; p< 0.01). There were no significant differences in serum levels at any time point. GDNF bioactivity was verified using a chick dorsal root ganglion cell bioassay
Our results showed that the topical route was efficacious for the delivery of GDNF to the retina and CSF, and suggest that this approach may prove to be an effective strategy for the treatment of certain retinal and CNS neurodegenerative disorders.
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