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G.A. Heatley, J. Kiland, T. Bunch, T. Nork, T. Perkins, P.L. Kaufman, B. Faha, R.W. Nickells; Evaluation of Presurgical Administration of Rad–p21 in Preventing Wound Healing After Trabeculectomy in Non–Human Primates: Potential for Interactions With Laser Trabeculoplasty . Invest. Ophthalmol. Vis. Sci. 2006;47(13):43.
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Prior studies of glaucoma surgery in rabbit and monkey models showed effective reduction of wound healing using adjunctive adenovirus–mediated delivery of the human p21 gene (rAd–p21) applied intraoperatively on a pledget. In this study, we examine the efficacy of the same virus delivered as a subconjunctival injection 24 hrs prior to trabeculectomy in monkeys with ocular hypertension.
Ocular hypertension was induced in one eye of 14 cynomolgus monkeys using argon laser ablation of the trabecular meshwork. Once IOP was stably elevated, 100 µL of reagent was injected subconjunctivally over the surgical site 24 hrs prior to trabeculectomy. Test reagents included 9e8 rAd–p21 particles ("low dose," n=4), 9e10 particles ("high dose," n=6), or vehicle (n=4). Trabeculectomy was performed the next day, with the surgeon masked to each treatment group. Eyes were monitored by regular slit lamp exams (SLE), optic disc stereophotography, and IOP measurements. Animals were killed 120 days post surgery and the surgical sites examined by histopathology.
SLE of eyes 24 hrs after injection, and prior to trabeculectomy, showed increased flare and cells in all treatment groups, suggesting that lasered eyes were susceptible to irritation caused by the injection protocol. All eyes showed similar time–dependent decreases in bleb height/extent after surgery and all failed to exhibit a sustained statistically significant drop in IOP. Low dose rAd–p21 showed some IOP control using qualitative outcome measures. Histology of the surgical site showed no correlation between the test reagents and prevention of a wound healing response.
In contrast to treatment at the time of glaucoma surgery, a subconjunctival injection of rAd–p21 the day before surgery had minimal effect in preventing wound healing. Laser ablation to elevate IOP may prime the wound healing response, which is exacerbated by a presurgical subconjunctival injection.
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