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Editors Selection IGR 7-1

Basic research

Comment by George Cioffi on:

11937 Effect of elevated intraocular pressure on endothelin-1 in a rat model of glaucoma, Prasanna G; Hulet C; Desai D et al., Pharmacological Research, 2005; 51: 41-50

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Prasanna et al. (14) present a series of experiments examining two diverse, yet potentially related, mechanisms for injury of the optic nerve. In a model of elevated intraocular pressure as previously described by Morrison, the authors examine endothelin-1 levels in the aqueous humor and optic nerve head, as well as endothelin receptor activity. The authors also correlate this with markers of glial activation. Elevated intraocular pressure is commonly used to model glaucoma in animals from mice to non-human primates. As well, endothelin-1, given either acutely or on a chronic basis, has been used to develop models of optic nerve injury. This investigation ties these mechanisms of optic nerve injury together. The authors observed large increases in the aqueous humor levels of endothelin-1, as well as increases of endothelin-1 in the optic nerve. Concomitant with these increases, the authors observed increases in endothelin receptorB activity and GFAP labeling, which may be indicative of astrocytic activation and possibly gliosis. The authors used extensive control animals, including sham surgical animals that experienced most of the surgical procedure but did not have elevated intraocular pressures. They felt that this indicated that increased levels of endothlin was the result of elevated intraocular pressure and not simply the result of the surgery.

Increased levels of endothelin was the result of elevated intraocular pressure and not simply the result of the surgery

However, these sham animals may not have had the same disruption of their blood-aqueous barrier as the elevated IOP animals, which may have played a role in the elevated endothelin levels seen in the high IOP model. Nonetheless, these findings are intriguing and may help to explain important observations of abnormal endothelin levels in human glaucoma. While this connection between the increased aqueous levels of endothelin-1 in the rat model of glaucoma and the optic nerve head findings remains to be defined, the concomitant astrocytic activation is also of interest. Retinal and optic nerve head astrocytic activity has been demonstrated to increase in both animal models of glaucoma, as well as human glaucoma. This, coupled with the co-localization of endothelin-b receptors, suggests that the glial-axonal relationship within the optic nerve may play an intimate role in the pathogenesis of glaucomatous optic neuropathy. Further studies investigating these findings will be of great interest and may offer a guide for possible therapeutic intervention in the future.

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