Enzymatic Liquefaction of Vitreous Humor in the Rat in vivo Increases Lens Nuclear pO2

Abstract

Purpose:: Other researchers have proposed that disruption of the normal vitreous gel may permit O₂ to travel more easily from the retina to the center of the lens where it may cause nuclear cataract (Barbazetto et al., 2004; Harocopos et al., 2004). We have used the enzyme microplasmin to liquefy vitreous humor and produce a posterior vitreal detachment (PVD) in vivo in guinea pigs (avascular retina), rats and cats (both with vascular retinas) to investigate the role of the vitreous humor in diminishing the amount of retinal O₂ reaching the lens.

Methods:: Vitreal and lens pO₂ levels were measured in vivo with a platinum-based fluorophore O₂ sensor (Oxford Optronix, Ltd.) 1-2 weeks after intravitreal injection of microplasmin. Scanning electron microscopy was used to confirm a microplasmin-induced PVD in the animals.

Results:: Vitreous liquefaction plus a PVD did not affect the normal low levels of O₂ in guinea pig vitreous humor (2mm Hg) and lens nucleus (0.5 mm Hg). However, for the rat (which possesses a vascular retina), vitreous liquefaction plus a PVD produced significant increases in pO₂ levels in the mid vitreous (35 mm Hg vs. 23 mmHg for the control; p<0.001) and center of the lens (9.4 mm Hg vs. 5.6 mm Hg for the control; p<0.05). A similar result was obtained for the mid vitreous of the cat (26.2 mm Hg vs. 16.3 mm Hg for the control; p<0.001). Liquefaction of vitreous humor with hyaluronidase, an enzyme which does not induce a PVD, did not produce elevated pO₂ levels in rat vitreous humor and lens nucleus, as did microplasmin. When animals with liquefied vitreous humor breathed 100% O₂, the times for O₂ to reach the mid vitreous and center of the lens, and climb to elevated concentrations in these regions, were dramatically decreased, compared to animals with normal vitreous.

Conclusions:: The results support the hypothesis that a normal, healthy vitreous gel, plus a tight vitreous humor/retina attachment, acts to impede the migration of O₂ from the retina to the center of the lens. The data have relevance to age-related human nuclear cataract, as well as vitrectomy-induced nuclear cataract.

Keywords: oxidation/oxidative or free radical damage • cataract • vitreous