Enzyme-induced posterior vitreous detachment in the rat produces increased lens nuclear pO 2 levels

Abstract

It has been proposed that disruption of normal vitreous humor may permit O 2 to travel more easily from the retina to the center of the lens where it may cause nuclear cataract (Barbazetto, I.A., Liang, J., Chang, S., Zheng, L., Spector, A., Dillon, J.P., 2004. Oxygen tension in the rabbit lens and vitreous before and after vitrectomy. Exp. Eye Res. 78, 917–924; Harocopos, G.J., Shui, Y.B., McKinnon, M., Holekamp, N.M., Gordon, M.O., Beebe, D.C., 2004. Importance of vitreous liquefaction in age-related cataract. Invest. Ophthalmol. Vis. Sci. 45, 77–85). In the present study, we injected enzymes intravitreally into guinea pigs (which possess an avascular retina) and rats (which possess a vascular retina) to produce either vitreous humor liquefaction plus a posterior vitreous detachment (PVD) (with use of microplasmin) or vitreous humor liquefaction only (with use of hyaluronidase), and 1–2 weeks later measured lens nuclear pO 2 levels in vivo using a platinum-based fluorophore O 2 sensor (Oxford-Optronix, Ltd.). Experiments were also conducted in which the animals were allowed to breathe 100% O 2 following intravitreal injection with either microplasmin or hyaluronidase in order to investigate possible effects on O 2 exchange within the eye. Injection of guinea pigs with either of the two enzymes produced no significant differences in lens pO 2 levels 1–2 weeks later, compared to controls. However, for the rat, injection of microplasmin produced a 68% increase in O 2 level in the center of the lens, compared to the controls (5.6 mm Hg increasing to 9.4 mm Hg, p < 0.05), with no corresponding effect observed following similar use of hyaluronidase. Treatment of guinea pigs with microplasmin dramatically accelerated movement of O 2 across the vitreal space when the animals were later allowed to breathe 100% O 2 (for example, O 2 traveled to a location directly behind the lens 5× faster than control; p < 0.01); however, the effect following treatment with hyaluronidase was significantly less. When microplasmin-injected rats breathed 100% O 2, the time required for O 2 to reach the center of the lens was 3× faster than control (0.4 min compared to 1.4 min, p < 0.01). The results have implication with regard to the occurrence of age-related PVD in the human, and a possible acceleration of maturity-onset nuclear cataract. In addition, enzymatic creation of a PVD to increase the rate of O 2 exchange within the vitreal space may have potential application for treatment of retinal ischemic disease.