glaucoma comprises a number of different pathomechanisms leading to a specific degeneration of the retinal ganglion cells and changes in the optic nerve head . primary open angle glaucoma is the most common form and affects about 1% of the western population . to date , the only defined risk factors for the development of primary open angle glaucoma ( poag ) are age and elevated intraocular pressure ( iop ) . patho - morphological correlations discussed for the elevated iop are the appearance of  plaque - like extracellular material  in the human trabecular meshwork [ 1 , 2 ] ,  empty spaces / giant vacuoles  in the juxtacanalicular region next to schlemm 's canal [ 35 ] , and the size of schlemm 's canal itself [ 6 , 7 ] . the active role of tm cells in this regulative process was considered due to their contractile properties [ 8 , 9 ] and due to intracellular volume regulation [ 1012 ] . interestingly , the increased production of aqueous humour alone seems not to be responsible for elevated intraocular pressure , although a number of therapies modify this input . in recent years , a broader understanding of intracellular volume regulation was gained by the description and investigation of specific ion channels and their molecular regulation . in this context early investigations of steroid hormone function in the eye were lead by clinical observations of iop elevation in one - third of the population after topical cortisone treatment [ 15 , 16 ] . persisting ocular hypertension can lead to a specific type of open angle glaucoma , the  cortisone - induced  glaucoma [ 17 , 18 ] with a typical morphological appearance [ 19 , 20 ] . interestingly , systemic elevation of cortisone can slightly increase iop but does not lead to a higher risk of glaucoma development . therefore , local mechanisms seem to play a crucial role . one of them is the 11-hydroxysteroid dehydrogenase ( hsd ) consisting of two isozymes with distinct different functions . hsd1 is the key enzyme for activation of cortisone ; hsd2 leads to inactivation of cortisone in specific tissues with aldosterone receptors which could also be activated by cortisone . to postulate an effect of cortisone , hsd1 for activation and the glucocorticoid receptor ( gr ) were described originally , but subsequent studies only confirmed the presence of gr [ 23 , 24 ] . from a functional point of view , glucocorticoids lead to an intracellular volume increase in trabecular meshwork cells [ 2527 ] and modify the extracellular matrix production [ 28 , 29 ] . most surprisingly , one of the extracellular matrix proteins affected is elevated in all human glaucomatous donor eyes [ 30 , 31 ] , but physiological studies recently questioned its role for elevation of trabecular meshwork resistance and iop [ 32 , 33 ] . thus the cellular volume increase effect of cortisone has the best evidence to be of pathophysiologic relevance for iop increase at present . for a long time , a second group of corticoid hormones , the mineralocorticoids , were not considered to play any significant function in the eye . however , early investigations mentioned that the aldosterone - antagonist spironolacton led to a decrease of intraocular pressure in glaucomatous patients . mirshahi and coworkers were the first to describe mineralocorticoid hormone receptors ( mr ) in the retina and all epithelial cells of the eye [ 36 , 37 ] . to consider specific aldosterone function , the presence of hsd2 next to the mr is necessary . the presence of mr and hsd2 in the trabecular meshwork is described controversially [ 2224 ] . mineralocorticoid effects are thought to be mediated by epithelial sodium channels ( enac ) [ 38 , 39 ] , which are also present at numerous places in the anterior eye segment [ 4043 ] . these channels might serve two different functions : one is fluid secretion from the ciliary epithelium ( increase of aqueous humour formation ) , and the other is regulation of the trabecular meshwork resistance by volume regulation of the trabecular meshwork cells . the first is the most widely suggested mechanism for aldosterone   since a consistent presence of mr and a strong evidence for the presence of hsd2 are reported in ciliary epithelium cells [ 2224 ] . if the trabecular meshwork is also a target tissue for aldosteron remains to be determined . a number of mouse models were established to study mineralocorticoid effects but no data exists about the eyes of these animals . the existing genetically altered mice show either an overexpression of the mr [ 4446 ] , a knockout of hsd2 , or alterations of the enac ion channels ( liddle 's syndrome ) [ 48 , 49 ] . unfortunately , there is no data in mouse eyes for the presence and distribution of mr and hsd2 . personal investigations on the distribution of enac in the mouse anterior eye segment showed intense staining for - and -enac , but no staining for -enac in the trabecular meshwork , while the ciliary epithelium showed only a weak staining reaction ( figure 1 ) . , mr overexpression led to massive changes in the anterior eye chamber due to epidermal atrophy in these nonviable puppets . unfortunately , these animals have a dba/2j background leading to changes in the chamber angle beginning at 3 months of age . personal investigations on the eyes of 6-months - old transgenic animals ( p1.hmr and p2.hmr from [ 44 , 45 ] ) show massive synechiae of the iris , atrophy of the ciliary body , strong pigmentation of the chamber angle , and loss of retinal ganglion cells . knockout of hsd2 was performed in c57/bl6 mice . the mouse model established for liddle 's syndrome there seems to be no effect of aldosteron on the -enac subunit in these animals . schlemm 's canal was widely open , trabecular meshwork cells were not swollen , abnormalities in the anterior and posterior eye segments could not be detected . since the normal mouse eye does not express the -enac subunit in the trabecular meshwork and inner eye surfaces , these results are not surprising . concluding , at this stage of research mouse models do not help to answer questions related to the role of mineralocorticoids in the eye . a number of conditions are known in the human associated with mineralocorticoid dysfunction . a relation to ocular pathologies was tested . hyperaldosteronism is a common , but rarely diagnosed condition ( estimated 1.53.5% of the entire population in germany ) . the induced high blood pressure can affect the eye but not in a glaucoma - specific way . apparent mineralocorticoid excess is a condition with lack of hsd2 and subsequently increased activation of mr . there is no report in the literature that any of the diagnosed patients suffered from either elevated iop or glaucoma . pseudohypoaldosteronism type 1 is related to a reduction of alpha enac function [ 56 , 57 ] . a communication with prof . hanukoglu ( tel aviv ) revealed that these persons do not complain of any specific eye symptoms . an extended ocular examination of his oldest patient at that time ( 19 years old ) showed normal intraocular pressure ( 17  mmhg ) , a normal anterior chamber including the chamber angle , and a normal oct of the nerve fibers in the retina . if this finding is related to a reduced function of the corneal endothelium remains to be determined . systemic application of mineralocorticoids to glaucoma patients shows no changes in the iop in most of the cases [ 58 , 59 ] . however , single individuals react with a high increase in intraocular pressure . unfortunately , these  mineralocorticoid - sensitive  persons are not further characterized . they could constitute a new subgroup of ocular hypertension or glaucoma patients , but more clinical data has to be collected to define these persons . the lack of general agonist effects combined with the mild iop decrease of antagonists   points to a possible role of mineralocorticoids for glaucoma therapy but not for general glaucoma pathophysiology . the narrowed role is also supported by the negative findings in the animal models and the various human conditions described above . the therapeutic effect of mineralocorticoid antagonists seems mainly mediated by a decrease of aqueous humour formation . one additional aspect of mineralocorticoid function is venoconstriction and thus an increase in postcapillary pressure [ 60 , 61 ] . venoconstriction could also be of relevance for elevated intraocular pressure as known from rat glaucoma models . . a different venous sensitivity could be a criterion for the above hypothesized mineralocorticoid - sensitive subgroup of humans . the proposed mechanisms by which mineralocorticoids play a role in glaucoma are summarized in figure 2 . while there is some evidence that the ciliary epithelium is affected by mineralocorticoids , the role of the trabecular meshwork cells and of the limbal veins remains to be determined . hopefully this paper attracts more scientists and clinicians for further research in the area of mineralocorticoids with respect to the pathogenesis of glaucoma .