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H. Liu, W. Xiao, A. Demetriades, S. Vinores, P. Campochiaro; Mouse Model of Post-Surgical Breakdown of the Blood-Retinal Barrier . Invest. Ophthalmol. Vis. Sci. 2003;44(13):353.
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Purpose: Postsurgical macular edema is a common cause of visual loss that occurs due to excessive and prolonged breakdown of the BRB. In order to elucidate molecular mechanisms involved and develop new treatments, a practical animal model is needed. The aim of this study was to develop and validate a mouse model of postsurgical breakdown of the BRB. Methods: Adult male C57BL/6 mice were anesthetized and under a dissecting microscope, two 25-gauge needles were inserted through the limbus into the lens of one eye. One needle was attached to infusion tubing from an elevated bottle of balanced salt solution (BSS), and the other needle was attached to suction tubing. The anterior portion of the lens was aspirated and then the needles were removed. At the end of the procedure, eyes were soft, but anterior chambers were formed. The fellow eye was left untreated. At 1, 2, 3, and 5 days after surgery, mice were given an intraperitoneal injection of 1 mCi/ gram body weight of [3H]mannitol. Sixty minutes after injection, the mice were euthanized and the retina to lung leakage ratio (RLLR) and the retina to renal leakage ratio (RRLR) were measured by a previously described technique. Results: Compared to control eyes (n=44; RLLR=0.452; RRLR=0.315), eyes that had partial lens removal had a significant increase in RLLR (1.579, p=0.001) and RRLR (1.161, p=0.002) at 24 hours after surgery (n=9), indicating severe breakdown of the BRB. Two days (n=9, 1.139, p=0.008; 0.862, p=0.016) and 3 days after surgery (n=12, 1.128, p=0.001; 0.735, p=0.002), there was still significant breakdown of the BRB, but by 5 days after surgery (n=9) there was no longer a significant increase in the RLLR (0.559, p=0.120) nor the RRLR (0.412, p=0.068) compared to control eyes. Conclusions: There is severe breakdown of the BRB after partial lens removal in mice, which peaks one day after surgery. The barrier is re-established over the next 2 days and by 5 days after the procedure there is no longer a significant increase in retinal vascular permeability. Future studies will be directed at identifying molecular signals responsible for breakdown of the BRB and at using the model to identify agents that prevent disruption of the BRB after ocular surgery.
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