Search

Objective: To determine the contribution of the breakdown of the blood-retinal barrier (BRB) as measured with magnetic resonance imaging in the development of retinal detachment in an experimental model of proliferative vitreoretinopathy., Methods: Contrast-enhanced magnetic resonance imaging was used to evaluate BRB breakdown in an intravitreal cell-injection model of proliferative vitreoretinopathy. Intravitreal injection of 2.5 x 10(5) homologous dermal fibroblasts produced specific disruption of the inner, or vascular, BRB., Results: Breakdown of the BRB was greatest in the first 3 days after injection, confirming previous work using fluorescein-based methods. Injection of 1 mg of intravitreal triamcinolone acetonide at the time of cell injection significantly reduced both BRB breakdown and the incidence of eventual traction retinal detachment. Eyes that did develop detachment had significantly greater leakage prior to its development than those that did not, regardless of steroid treatment., Conclusions: Quantitation and definitive localization of BRB leakage with magnetic resonance imaging provides a better understanding of the relationship between BRB compromise and the development of retinal detachment in this frequently used model.

Animals were given a 0.1-mL intravitreous injection of various agents and followed up with frequent ophthalmoscopic examinations. Fundus photographs were performed before injection and at six and 24 hours after injection. Vascular caliber was assessed by a previously described technique of performing measurements on fundus photographs taken and projected in a standardized fashion. No significant vascular dilation was identified for vehicle alone, carbachol, histamine, isoproterenol hydrochloride, or bradykinin. Mild dilation within one hour, but not persisting for 24 hours, was noted for dibutyryl cyclic adenosine monophosphate. Prominent dilation within one hour, becoming maximal by five hours but not persisting for 24 hours, was noted for adenosine, dipyridamole, and sodium nitroprusside. The adenosine-induced vasodilation was effectively blocked by an adenosine receptor antagonist, BW-A1433U. N-ethylcarboxamidoadenosine (NECA), a nonspecific adenosine selective agonist, was a much more potent vasodilator than two relatively selective A1 adenosine agonists, N6-cyclopentyladenosine and N6-phenylisopropyladenosine, suggesting that A2 receptors are involved. The vascular dilation caused by adenosine, dipyridamole, and particularly NECA, but not nitroprusside or dibutyryl cyclic adenosine monophosphate, was accompanied by retinal hemorrhages, producing a picture reminiscent of some features of ischemic retinopathies. This study suggests that adenosine may be an important mediator of vasodilation, and therefore blood flow, in the retina.

Rabbits were given an intravitreous injection of 5.0 x 10(5) rabbit retinal pigment epithelial (RPE) cells, human RPE cells, or human dermal fibroblasts in one eye and an injection of vehicle alone in the other eye. Some rabbits were treated with retinal cryopexy or intravenous sodium iodate on the day before injection. Vitreous fluorophotometry (VFP) and fundus examinations were performed before and at various times after cell injections. Retinal detachments were graded by premortem ophthalmoscopic examinations and postmortem gross pathologic examinations. Eyes injected with cells had higher VFP readings than eyes injected with vehicle at all time points. Eyes injected with fibroblasts or rabbit RPE had significantly higher mean VFP values before the onset of retinal detachment than those injected with human RPE cells. Within each group, high levels of fluorescein leakage in the first week correlated well with severity of subsequent traction retinal detachment and the fibroblast and rabbit RPE groups had more severe detachments than the human RPE group. Treatment with cryopexy or sodium iodate resulted in higher VFP readings, a higher frequency of retinal detachments, and detachments that occurred earlier and that were more severe. These data demonstrate that intravitreous cells cause blood-retinal barrier breakdown in rabbits and that the amount and duration of this breakdown are important variables in retinal detachment formation.

Pigmented rabbits were anesthetized and given an intravitreous injection of 0.1 mL of a test substance or vehicle alone. Vitreous fluorophotometry was performed before injections and at various time points after injections. Compared with pretreatment scans, vehicle-injected eyes showed no change in intravitreous fluorescein sodium leakage at 6 and 24 hours after injection. Injection of adenosine (10(-2) mol/L) resulted in fluorescein leakage that was significantly greater than that which occurred in control eyes at 6 hours after injection, but returned to baseline at 24 hours. This effect was significantly attenuated by an adenosine receptor antagonist (BW-A1433U), suggesting that it was mediated by specific adenosine receptors. A nonselective adenosine receptor agonist, N-ethylcarboxamidoadenosine, and two relatively A1 selective receptor agonists, N6-cyclopentyladenosine and N6-phenylisopropyladenosine, also caused dose-dependent intravitreous fluorescein leakage. The relative order of potency was N-ethylcarboxamidoadenosine much greater than N6-phenylisopropyladenosine, which was greater than N6-cyclopentyladenosine, implicating A2 adenosine receptors. Intravitreous injection of dipyridamole, an adenosine uptake inhibitor, caused enhanced fluorescein leakage, presumably from extracellular accumulation of endogenous adenosine. The results of this study suggest that adenosine may be a mediator of blood-retinal barrier breakdown.