Experimental scleral cross-linking increases glaucoma damage in a mouse model

Abstract

Purpose: To assess the effect of a scleral cross-linking agent on susceptibility to glaucoma damage in a mouse model.

Methods: CD1 mice underwent 3 subconjunctival injections of 0.5 M glyceraldehyde (GA) over 1 week, then had elevated intraocular pressure (IOP) induced by anterior chamber bead injection. Control mice had buffer injection in one experiment and no injection in a second trial. IOP was monitored by Tonolab and retinal ganglion cell (RGC) loss was measured by histological axon counting. To rule out undesirable GA effects, we performed electroretinograph (ERG) and detailed retinal histology. The mechanical effects of GA were measured by inflation testing and the degree of cross-linking was measured by ELISA.

Results: GA exposure had no detectable effects on RGC number, retinal structure or function by histology or ERG. GA treatment produced a steeper pressure—strain behavior in the sclera by in vitro inflation testing. In experiment 1, GA-treated eyes 62% RGC loss compared to 34% loss in buffer controls (median, p = 0.01 regression model adjusting for IOP exposure). In experiment 2, GA injected eyes lost 45% of RGC axons compared to 23% for uninjected controls (mean, p = 0.049, multivariable regression). Axial length and width increased with elevated IOP, significantly more in buffer-injected than in GA eyes (10.5% vs. 7.7% mean length increase, p = 0.05, t test).

Conclusions: This is the first report that a therapeutic scleral alteration of sclera, by GA cross-linking, increased susceptibility to RGC damage in mice. Successful glaucoma neuroprotection through modulation of scleral responses may be possible by identifying beneficial changes in its biomechanics.

Keywords: 531 ganglion cells • 708 sclera • 615 neuroprotection