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Editors Selection IGR 14-3
Basic Research Animal Studies: Dexamethason-induced OH in mice
Comment by Abbot Clark on:
27057 Increased intraocular pressure in mice treated with dexamethasone., Whitlock NA; McKnight B; Corcoran KN et al., Investigative Ophthalmology and Visual Science, 2010; 51: 6496-6503
Glucocorticoid (GC) therapy can lead to ocular hypertension (OHT) and secondary open-angle glaucoma in susceptible individuals. This steroid glaucoma mimics many of the clinical features of POAG and also causes similar biochemical and cellular changes in the trabecular meshwork (TM). Many groups have shown that GCs have a wide variety of effects on the TM, but we do not know which changes are responsible for GC-OHT. GCs also cause OHT in several different animals, including rabbits, nonhuman primates, cats, cows, sheep, and rats. An exciting new study by Whitlock et al. (1624) now reports the generation of dexamethasone-induced OHT in mice.
OHT in mice can be induced by dexamethasone
DEX was continuously delivered by a subcutaneously implanted osmotic minipump, which caused a reproducible and statistically significant 23-28% increase in IOP. Pressure elevations would likely be even greater if mouse IOPs were measured in conscious mice and at nighttime. Since the DEX was systemically administered, it was not surprising that these mice also showed systemic side effects associated with GC therapy, including loss in body weight, systemic hypertension, and leukopenia. However, Whitlock and colleagues clearly showed that there was no correlation between DEX-induced IOP elevation and these systemic side effects, suggesting that these side effects were not responsible for the DEX mediated IOP elevation. Having a mouse model of GC-induced OHT is very exciting for a number of reasons. Not all mice in the mixed B6.129 background developed DEX-OHT, suggesting potential differences in steroid responsiveness in mice.
Not all mice developed DEX-OHT, suggesting potential differences in steroid responsiveness in mice
Genes regulating this responsiveness could be mapped and identified, offering new glaucoma candidate genes or potential genetic tests for steroid responsiveness, which now must be determined empirically. In addition, the power of mouse genetics can be used to directly determine which DEX-induced genes/pathways are responsible for the development of GC-induced OHT.
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