Purchase this article with an account.
L. Leo, A. Gvritishvili, Y. Liu, J. Tombran-Tink; Corneal Application of PEDF78-121 Reduces Ischemic Injury in the Retina. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4516.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Intravitreal injections of the PEDF protein or virally delivered PEDF gene can protect photoreceptors and retinal ganglion cells from degeneration. We have shown that a small PEDF fragment, PEDF78-121, mimics the neuroprotective actions of PEDF in an ischemic model of retinal degeneration. Here we examined whether this small peptide can reach the posterior eye when applied to the cornea in concentrations that reduces ischemic injury to the retina.
5 ug of fluorescently labeled PEDF78-121 was applied for 1-3 h on the cornea of rodent eyes to determine if the peptide penetrates the cornea and reaches the posterior segment of the eye. Concentrations of the labeled peptide was measured spectrophotometrically in ocular fluids and fluorescence in the retina determined by confocal microscopy. Ischemic injury was carried out using 160mm Hg for 1h and the injured and control non-injured eyes were immediately treated with topical application of unlabeled peptide or vehicle alone to test neuroprotective efficacy. Cell death, glial response, and neuroprotective signaling were examined after injury and topical delivery of PEDF78-121
Labeled PEDF 78-121 completely penetrates the cornea and is detected in the central retina in the RGC layer by 2h. The RPE and choroidal vessels also show strong fluorescence after ~4h of topically applied PEDF78-121. The labeled peptide was detected in the vitreous and aqueous as early as 30 min with approximately 60% of the peptide present in these compartments by 2h. A reduction in GFAP expression and a decrease in activated Caspase 3 were evident in the injured eye 24 hr after the topical peptide treatment compared to controls. Topical PEDF78-121 activates Stat3 and AKT neuroprotective signaling and reduces phosphorylation of ERK1/2 within 60 min of reaching the ischemic retina. RGC’s and retinal layer thickness were also preserved compared to non-treated injured eyes.
The neuroprotective PEDF78-121 peptide can be delivered in therapeutic doses to the retina by corneal application. These results suggest that a simple and effective way to deliver small neurotrophic factors to treat retinal degenerative conditions is by eye drop formulations.
This PDF is available to Subscribers Only