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Rachael Elaine Warrington, Peter J Coffey, Monte J Radeke, Geoffrey P Lewis; Inhibition of retinal injury-induced glial proliferation by intraocular administration of Palbociclib. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4224.
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© ARVO (1962-2015); The Authors (2016-present)
Ocular trauma can lead to retinal detachment and subsequent vision loss, which significantly affects a person’s quality of life. At present, the only effective treatment for retinal detachment is surgical reattachment, however visual acuity may not be restored and secondary scarring known as proliferative vitreoretinopathy (PVR) may occur, leading to further visual complications. We performed a quantitative study to determine if the drug Palbociclib, a CDK4/6 inhibitor, can prevent detachment-induced glial proliferation. For comparison, we used the drug Palomid 529, an inhibitor of the Akt/mTOR pathways, previously shown to reduce proliferation and glial scarring following retinal detachment (IOVS 2009; 50: 4429-4435).
Retinal detachments were created in right eyes of New Zealand white rabbits and drugs were administered by intravitreal injection immediately after detachment. Two therapeutic concentrations were tested (Palbociclib: 24 and 120 µg; Palomid 529: 120 and 600 µg) with three replicates for each treatment. Eyes treated with vehicle alone (balanced salt solution, BSS), non-operated eyes, and non-detached regions served as controls. Animals were euthanized three days after detachment and the effect of each drug was assessed using immunohistochemistry. Significance was assessed using a Student’s T-test.
In drug treated eyes, the highest dosage significantly reduced the average number of Ki67 positive Müller cells (mean±SEM: Palbociclib 0.04±0.04/mm of retina, n=3, P=0.001 and Palomid 529 2.43±1.00/mm of retina, n=3, P=0.028). In comparison, for the lower dose treatment only Palbociclib significantly decreased Ki67 labelled Müller cells (mean±SEM: Palbociclib 3.09±0.93/mm of retina, n=3, P=0.043 and Palomid 529 4.41±1.21/mm of retina, n=3) compared to vehicle injected controls (mean±SEM: BSS 6.60±1.04/mm, n=6). Neither drug prevented the increase in the number of microglia or macrophages following detachment. No adverse effects on gross retinal morphology were noted with either treatment.
Palbociclib, an FDA approved cancer therapeutic, is highly effective at reducing the proliferation of glial cells induced by retinal detachment. This drug, together with Palomid 529, which also suppresses glial scarring, may be good candidates for a combinatorial strategy to treat proliferative diseases such as PVR that often occurs following retinal injury.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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