TY - JOUR
T1 - Experimental scleral cross-linking increases glaucoma damage in a mouse model
AU - Kimball, Elizabeth C.
AU - Nguyen, Cathy
AU - Steinhart, Matthew R.
AU - Nguyen, Thao D.
AU - Pease, Mary E.
AU - Oglesby, Ericka N.
AU - Oveson, Brian C.
AU - Quigley, Harry A.
N1 - Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - The purpose of this study was to assess the effect of a scleral cross-linking agent on susceptibility to glaucoma damage in a mouse model.CD1 mice underwent 3 subconjunctival injections of 0.5M glyceraldehyde (GA) in 1 week, then had elevated intraocular pressure (IOP) induced by bead injection. Degree of cross-linking was measured by enzyme-linked immunosorbent assay (ELISA), scleral permeability was measured by fluorescence recovery after photobleaching (FRAP), and the mechanical effects of GA exposure were measured by inflation testing. Control mice had buffer injection or no injection in 2 separate glaucoma experiments. IOP was monitored by Tonolab and retinal ganglion cell (RGC) loss was measured by histological axon counting. To rule out undesirable effects of GA, we performed electroretinography and detailed histology of the retina. GA exposure had no detectable effects on RGC number, retinal structure or function either histologically or electrophysiologically. GA increased cross-linking of sclera by 37% in an ELISA assay, decreased scleral permeability (FRAP, p=0.001), and produced a steeper pressure-strain behavior by invitro inflation testing. In two experimental glaucoma experiments, GA-treated eyes had greater RGC axon loss from elevated IOP than either buffer-injected or control eyes, controlling for level of IOP exposure over time (. p=0.01, and 0.049, multivariable regression analyses). This is the first report that experimental alteration of the sclera, by cross-linking, increases susceptibility to RGC damage in mice.
AB - The purpose of this study was to assess the effect of a scleral cross-linking agent on susceptibility to glaucoma damage in a mouse model.CD1 mice underwent 3 subconjunctival injections of 0.5M glyceraldehyde (GA) in 1 week, then had elevated intraocular pressure (IOP) induced by bead injection. Degree of cross-linking was measured by enzyme-linked immunosorbent assay (ELISA), scleral permeability was measured by fluorescence recovery after photobleaching (FRAP), and the mechanical effects of GA exposure were measured by inflation testing. Control mice had buffer injection or no injection in 2 separate glaucoma experiments. IOP was monitored by Tonolab and retinal ganglion cell (RGC) loss was measured by histological axon counting. To rule out undesirable effects of GA, we performed electroretinography and detailed histology of the retina. GA exposure had no detectable effects on RGC number, retinal structure or function either histologically or electrophysiologically. GA increased cross-linking of sclera by 37% in an ELISA assay, decreased scleral permeability (FRAP, p=0.001), and produced a steeper pressure-strain behavior by invitro inflation testing. In two experimental glaucoma experiments, GA-treated eyes had greater RGC axon loss from elevated IOP than either buffer-injected or control eyes, controlling for level of IOP exposure over time (. p=0.01, and 0.049, multivariable regression analyses). This is the first report that experimental alteration of the sclera, by cross-linking, increases susceptibility to RGC damage in mice.
KW - Collagen
KW - Cross-linking
KW - Extracellular matrix
KW - Glaucoma
KW - Glyceraldehyde
KW - Mouse
KW - Retinal ganglion cell
KW - Sclera
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U2 - 10.1016/j.exer.2014.08.016
DO - 10.1016/j.exer.2014.08.016
M3 - Article
C2 - 25285424
AN - SCOPUS:84907984855
SN - 0014-4835
VL - 128
SP - 129
EP - 140
JO - Experimental eye research
JF - Experimental eye research
ER -