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Alireza Hosseini, Jorge L. Jacot, Frank A. Lattanzio, Jr., Karl A. Schellenberg, Sandeep S. Samudre, Patricia B. Williams; Evaluation Of Anti-tubulin Agents For The Prevention Of Vasculopathy In A Rat Model Of Retinopathy Of Prematurity. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3979.
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Retinopathy of prematurity (ROP) is a major cause of neonatal vision loss, accounting globally for approximately 50,000 cases annually of neonatal blindness. This study valuated the efficacy of anti-tubulin drugs, OC-10X and thalidomide, in the prevention of vasculopathy in a hyperoxia-hypoxia induced rat model of ROP.
Rat pups from timed-pregnant Sprague-Dawley rats were randomized and placed in an oscillating oxygen chamber (FiO2 between 50% and 10%, cycling every 24 hours) for the first 14 days postnatally. On post-natal day 15 pups were exposed to room air (21% oxygen) and separated into three experimental groups (n=10 per group) during the vasoproliferative phase of ROP (post natal days 20 to 28). Experimental groups were: 1) Topical 1% OC-10X (tid), 2) Topical vehicle control (tid) and 3) Oral gavage of 100mg/kg thalidomide (qd). Rat pups were euthanized and enucleated at post-natal days 20, 24 or 28. The extent of retinal neovascularization was assessed by computer-assisted morphometry in fixed retinal whole mounts stained with ADPase. Retinal vasculopathy was evaluated using a quantitative severity scale (0-5) for the following parameters: 1) Area of avascularity, 2) Extent of vascular tufts, 3) Hemorrhages, and 4) Vessel tortuosity. While avascularity and vascular tortuosity demonstrates the model development, the extent of vascular tufts and hemorrhages are the areas expected to be effected by antiangiogenic treatments.
A demonstrable trend in reduction of the vascular tufts and incidence of retinal hemorrhage from both the OC-10X and thalidomide treated groups relative to vehicle was observed. While avascularity and vascular tortuosity confirmed the model development, the extent of vascular tufts and hemorrhages were the areas expected to be affected by antiangiogenic treatments.
These preliminary findings suggest that structurally diverse anti-tubulin agents may impart beneficial effects on measurable end-points of ROP vasculopathy, such as vascular tufts and hemorrhage, which could have a clinical impact on improving visual outcome.
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