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Z.Z. Chen, B. Faha, S. Siagel, Q. Nguyen, D. Maneval; Preventing Glaucoma Filtration Surgery Failure by Subconjunctival Delivery of a Recombinant Adenovirus–Encoding p21WAF1/CIP1(rAd–p21): . Invest. Ophthalmol. Vis. Sci. 2005;46(13):56.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To evaluate the effect of rAd–p21on proliferation of conjunctival fibroblasts and assess effects on inhibition of wound healing post glaucoma filtration surgery (GFS) following a pre–surgical subconjunctival injection of rAd–p21 in the rabbit model. Methods: Test 1. 15 rabbits were randomly assigned to 3 treatment groups (5/group). 24h before GFS, rabbits in groups 1 and 2 received single subconjunctival injections of rAd–p21 (100µl; 1e12 particles/ml) or Tris glycerol excipient (100 µl), respectively. Animals in group 3 received mitomycin C (MMC,100µl of 0.4mg/ml) intraoperatively. All animals underwent unilateral (od) sclerectomy surgery using a 1.5 mm scleral punch. IOP from both surgical and non–surgical eyes was measured on d1, d3, d7, twice weekly up to 4 weeks and then once a week up to 11 weeks post surgery. Surgical failure was defined as IOP measurements greater than or equal to the baseline IOP group mean ± 2 mm Hg. Animals were sacrificed up to week 11 post surgery and eyes were enucleated for histological analysis. Test 2. 24 rabbits were assigned to 3 treatment groups (8/group) with the same dose, delivery routes and surgical procedures as in Test 1: group 1 MMC (100µl of 0.4mg/ml), group 2 rAd–p21 (100µl of 7.8 e11 particles/ml) and group 3 PBS (100 µl). Animals were sacrificed on day 1, 3, 7, and 14 post sclerectomy. The eyes were collected and immunostained for p21 transgene expression. Sections were also stained for BrdU and Mib–1 markers of proliferation. BrdU and Mib–1 staining was quantified using Image Analysis software. Results:Test 1. Significant differences in mean IOP were observed between the MMC and Tris glycerol treated animals (p < 0.001), and between the rAd–p21 and Tris glycerol groups (p < 0.05). Test 2. Peak BrdU incorporation occurred 3 days after filtration surgery in control–treated animals. Mib–1 and BrdU staining was negative in the conjunctiva in p21 positive staining serial sections at d3 post surgery. Conclusions:rAd–p21 inhibited fibroproliferation after glaucoma surgery in rabbits following subconjunctival administration. These finding support further investigation of rAd–p21 as a potential adjunctive therapy for inhibition of wound healing after glaucoma surgery.
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