Experimental Glaucoma and Optic Nerve Transection Induce Simultaneous Upregulation of Proapoptotic and Prosurvival Genes

Abstract

Members of the p-53 signal transduction pathway are significantly involved in glaucoma and ONT. The endogenous caspase inhibitor IAP-1 is upregulated simultaneously, possibly as part of an intrinsic neuroprotective mechanism. Changes in glaucoma are gradual and last long after IOP returns to normal.

A dietary combination of omega-3 and omega-6 polyunsaturated fatty acids is more efficient than single supplementations in the prevention of retinal damage induced by elevation of intraocular pressure in rats

“…In this study, we observed a substantial rise in IOP that started the first day after laser photocoagulation of the episcleral veins, limbus and trabecular meshwork. Twenty-four hours after the intervention, IOP values were higher than those observed in chronic glaucoma models [30,31], suggesting that our model is more an ischemia model than a glaucoma model. Some similarities with models of retinal ischemia were observed in our study, such as alterations of visual function as shown by the decrease in the ERG a-and b-wave amplitudes [7,32] and the shrinkage of the outer retinal layers [33,34].…”

Differential Gene Expression in Glaucoma

“…The up-regulation of STAT3 seems to be relatively specific for glaucomatous damage, as it was not observed after optic nerve transection or ischemia/reperfusion injury Yang et al 2007). A simultaneous up-regulation of proapoptotic and antiapoptotic genes (like the caspase inhibitor IAP1) was also observed in a rat model of increased IOP and optic nerve transection (Levkovitch-Verbin et al 2006b). This suggests that there is a balance between protective and detrimental processes when the ganglion cells are threatened by injury.…”

“…Conceivably, this balance could be tilted in favor of the protective side by timely therapeutic intervention. As an example of such a strategy, minocycline, an anti-inflammatory and neuroprotective second-generation tetracycline, was found to delay retinal ganglion cell death in a rat model of glaucoma (Levkovitch-Verbin et al 2006a). Both ocular hypertension and optic nerve transection lead to upregulation of immediate early response genes.…”

The relationship of TP53 and GRIN2B gene polymorphisms with risk of occurrence and progression of primary open-angle glaucoma in a Polish population

“…The quantitative changes of these gene products may lead to the initiation of apoptosis [17]. The study of an experimental model of glaucoma showed that TP53 is overexpressed in retinal ganglion cells compared to healthy subjects [18]. Moreover, the expression of TP53 is observed in RGCs under conditions that would stimulate apoptosis [19,20].…”