**4. Conclusion**

This chapter deals with one of the urgent problems of modern ophthalmology: revealing the mechanisms underlying induction of primary open-angle and pseudoexfoliative glaucoma. Till nowadays the problem remains rather actual, as the issue is open to discussion: what are the regional mechanisms underlying the disorders in functions of the trabecular apparatus of the angle of anterior chamber of an eye and in the increase of intraocular pressure at the mentioned disease case.

One of severe complications of glaucoma is the steady persistent increase of intraocular pressure that is fraught with compression of the head of optic nerve that results in its partial or complete atrophy with the partial and/or complete sight loss. Currently, the majority of specialists engaged in clinical and experimental ophthalmology are inclined to the opinion that the increase of intraocular pressure is not the consequence of general hemodynamic disorders resulting from the permeability increase in hematoophthalmic barrier, but rather originates from pathological processes occurring in the membranes and chambers of an eye.

cytotoxic lymphocytes subpopulations (T-suppressors and T-killers) is determinant in processes of forming intercellular correlation among different lymphocytic subpopulations localized in eye membranes, hence ensuring reactions underlying ACAID. However, it is not excluded that the sphere of TGFβ-2 activity under conditions of norm is more versatile, as *in situ* produced mentioned cytokine directly and/or indirectly (activating the synthesis of fibronectin and IGF-1 in a mediated manner) participates in processes of maintaining the drainage function of trabecular meshwork, thus ensuring the constant level of intraocular pressure. Apparently, the above-mentioned mediatory effects of TGFβ-2 are strictly dosedependent, as under conditions of pathology (in the given case: at senile and, especially, at the complicated cataracts) a significant elevation of TGFβ-2 in eye membranes brings to trabecular

meshwork dysfunction; the latter is fraught with the increase of intraocular pressure.

possibility of PgE2 participation in processes of intraocular pressure regulation.

meshwork, in mechanisms ensuring the drainage function of an eye.

senile non-complicated cataract.

90 Glaucoma - Basic and Clinical Aspects

of the eye.

**4. Conclusion**

mentioned disease case.

The analysis of our own research results in the context of available publications allows to consider the important role of TGFβ-2 and IGF-1, which are produced in cornea and trabecular

The facts of detection of receptors to PgE2in cells of trabecular meshwork and sclera allow

The high level of PgE<sup>2</sup> found by us in aqueous humour allows possibility of its participation in processes of the impaired drainage function and increase of intraocular pressure at cataracts proceeding on the background of primary open-angle glaucoma pseudoexfoliative glaucoma. The following phenomenon of no less importance should specially mentioned: high levels of fibronectin IGF-1 and PgE2 in the aqueous humour of patients under study were pathogno‐ monic for the course of the primary open-angle glaucoma and not for cataracts, as in this latter case all the indices studied in aqueous humour were much lower than analogous indices at

Our research revealed a direct correlation dependence between the high level of cortisol, on the one hand, and the content of sodium and calcium ions, on the other hand. Based on the results obtained a conclusion might be drawn that the increase of intraocular pressure in persons with complicated cataracts on the background of glaucoma is mostly conditioned by impairment of ion transfusion between the ciliary body and aqueous humour and the proc‐ esses of cortisol "hyperproduction" by hormone-producing cells in post-barrier membranes

This chapter deals with one of the urgent problems of modern ophthalmology: revealing the mechanisms underlying induction of primary open-angle and pseudoexfoliative glaucoma. Till nowadays the problem remains rather actual, as the issue is open to discussion: what are the regional mechanisms underlying the disorders in functions of the trabecular apparatus of the angle of anterior chamber of an eye and in the increase of intraocular pressure at the

In line with the modern views, processes underlying the increased intraocular pressure originate in the eye structures as such: in connective-tissue, epithelial and endothelial cells of the ciliary body, cornea, retina, lens, trabecular apparatus of the angle of the anterior chamber of an eye. These cells possess selective secretory activity in the aspect of producing a number of biologically active substances exerting direct and/or indirect action to the processes regulating intraocular pressure.

Moreover, numerous pathological processes proceeding in case of primary open-angle glaucoma at the site of eye membranes are fraught with the infringement of chamber humour osmolarity; furthermore, one of mechanisms increasing the volume of aqueous humour and not infrequently hindering its outflow is the impaired K+ /Na+ balance in favour of the accu‐ mulation of this latter in the anterior chamber of an eye.

Available literary data of the last 30 years which discuss mediatory functions realized by cells of fibroblastic, epithelial and endothelial line in a ciliary body, cornea, retina, lens, a trabecular network formed a basis for carrying out the research directed at clarification of a role of *in situ* produced fibronectin, IgF-1 and a cortisol at primary open-angle glaucoma.

The drainage function of trabecular meshwork of an angle of the anterior chamber of an eye is an active process, in which the leading role belongs to secretory cells of this network. As it was specified above, secretory cells of the trabecular meshwork develop TGFβ-2, fibronectin and an insulin-like growth factor -1, PgЕ2. It is not excluded that the mentioned substances play an important role in ensuring drainage function of a trabecular meshwork, and thus, to a certain extent, in maintenance of an optimum level of the intraocular pressure.

For this reason, high indices of fibronectin and IGF-1 found in aqueous humour of patients with primary open-angle glaucoma testify in favor of hypersecretion of mentioned cytokines by cells of a trabecular meshwork. The presence of fibronectin and insulin-like growth factor-1 high concentrations at the primary open-angle glaucoma, and also at pseudoexfoliative glaucoma, testifies to violation of drainage function of a trabecular meshwork of an angle of the anterior chamber of an eye; this latter, to a certain extent, preconditions the high level of intraocular pressure. At the same time, the specific weight of fibronectin and insulin-like of growth factor -1 in hypertension formation in the aqueous humour is far from being equivalent, as on the one hand, fibronectin level in aqueous humour of patients from investigated groups II and III 10 times exceeds concentration of insulin-like growth factor-1 in the same liquid, on the other hand, as known, the weight of soluble fibronectin makes 440.000-150.000 D, while the mass of insulin-like growth factor-1 is 7.649 D [*Panteleev M. A. et al., 2011*].

Thus, on the basis of the analysis of literary data and carried-out own research it is possible to conclude that at glaucomas the infringement of drainage function and increase of intraocular pressure is in many respects caused by high concentration of fibronectin and, partially, insulinlike growth factor-1 in the intraocular liquid.

established by us on impaired ionic balance between eye membranes and the intraocular

Modern Aspects of Glaucoma Pathogenesis Local Factors for Development of Primary Open-Angle Glaucoma…

considered from positions of the broken ionic balance between specific membranes of an eye and intraocular liquid, and not as a result of the general disorder of electrolytes composition in blood of experimental animals, because the level of studied electrolytes in blood serum was

Secondly, the high level of a cortisol found by us in aqueous humour can serve one of possible causes of infringement of the ionic balance. This assumption appears very reasonable, as it is known that high concentrations of cortisol in separate membranes of an eye lead to ionic imbalance in connection with enhanced inflow of ions of sodium in aqueous humour that

Thirdly, it is not excluded that realization of hormonal and cytokine-dependent processes conditioned by regional shifts in the content of cortisol, prolactin, fibronectin, insulin-like growth factor-1 at cataracts proceeding on the background of primary open-angle glaucoma and pseudoexfoliative glaucoma, is caused by activation of calcium-dependent reactions in

It is considered established that the pseudoexfoliative syndrome represents itself as a provok‐ ing factor for development of the open-angle glaucoma, the course of which has a progressing character and is characterized by high resistance to carried-out medicamentous therapy and an unfavourable forecast [*Prince A.J, Ritch R., 1986; Streeten B.W. et al., 1990; Tarkkanen A. et al.,*

One of severe complications at development of a pseudoexfoliative syndrome is cataract as

The impairment of immunological tolerance (of immunological privileges of an eye – ACAID) acts as an initiating factor for development of pseudoexfoliative syndrome [*Takhchidi K.P. et.*

It is not excluded that in pathogenesis of pseudoexfoliative syndrome emergence are also involved the local hormonal-mediatory mechanisms connected not with the operational intervention, but rather with infringement of processes of synthesis and secretion of such cytokines as TgFβ-2, IGF-1 and, first of all, fibronectin in cornea, ciliary body and trabecular

At a pseudoexfoliative syndrome essential physical and chemical changes occur in aqueous humour: the concentration of proteins considerably raises, including fibronectin as well [*Takhchidi K.P. et al., 2010*]. At the same time, shifts found by us in aqueous humour of patients with cataract on the background of pseudoexfoliative glaucoma, in many respects depend on the character of disease course: not so much of cataract, as glaucoma and the pseudoexfoliative syndrome. It is not excluded that in this studied group the high level of fibronectin in aqueous humour in many respects depends on features of pseudoexfoliative syndrome development.

and Ca++ levels observed by us in aqueous humour should be

http://dx.doi.org/10.5772/55037

93

liquid.

Firstly, the increase of Na+

within the limits of control values.

secretory cells of eye membranes.

*2002; Takhchidi K.P. et al., 2010*].

*al., 2010*].

meshwork of synthesis.

well [*Küchle M. et al., 1997; Puska P., Tarkkanen A., 2001*].

results in an increase of intraocular pressure.

As it was noted above, the content of PgЕ2 considerably increases in aqueous humour of patients with primary open-angle glaucomas and pseudoexfoliative glaucomas.

There is scanty literature about the synthesis of prostaglandins in eye membranes. Local synthesis of prostaglandins is found out only in cells of crystalline lens that was proved by research of O. Nishi et al. (1992) in model experiments *in vitro*: at cataract the extracted lens in the course of operation was located on incubation medium. With the increase of incubation terms the content of prostaglandins Е<sup>2</sup> in the incubation environment considerably increased. At the same time, in a number of eye membranes, the ciliary body, sclera and the trabecular meshwork of an angle of the anterior chamber of an eye receptors to prostaglandins Е2 were found [*Toris C.B. et al., 2008*].

It is not excluded that the high content of PgЕ<sup>2</sup> in aqueous humour is fraught with an increase of intraocular pressure at glaucomatous patients, as according to [*Podos S.M. et al., 1972 a; b; Podos S.M., 1976 a; b; c*], PgЕ2 takes an active part in maintenance of drainage function of an eye.

It is known that ionic balance in liquid media of an organism (blood, spinal, gingival, synovial and intraocular liquids) is a necessary condition for maintenance of the osmotic pressure.

The anterior and posterior chambers of an eye are main depots; water makes about 93% and a very insignificant share make proteins. It is considered established that the delay of outflow of aqueous humour or its intensive more "production" promotes considerable elevation of pressure inside an eye.

Thus, one of the factors leading to increase of intraocular pressure at glaucomas is the increase of osmolarity of intraocular liquid.

It is considered to be established long ago that at anterior open-angle glaucoma in aqueous humour there are serious impairments in its ionic structure that was shown by disorders in functioning of sodium ‒ potassium pomp, with the superfluous accumulation of sodium ions.

In our research as demonstrated by the results of ion-selective analysis, at primary open-angle glaucomas and pseudoexfoliative glaucomas rather high indices of ions of sodium and calcium and low indices of potassium were determined in aqueous humour, as compared with the indices defined in aqueous humour of patients with senile not complicated cataracts.

The similar imbalance, being shown as superfluous accumulation of sodium and calcium in aqueous humour, complicates normal outflow of aqueous humour from the anterior chamber of an eye that, in its turn, is fraught with the increase of intraocular pressure.

Without considering the questions connected with mechanisms of shifts found by us regarding electrolytes content in aqueous humour (that was not an actual problem of the present research), nevertheless we consider expedient to discuss some aspects connected with the fact established by us on impaired ionic balance between eye membranes and the intraocular liquid.

Thus, on the basis of the analysis of literary data and carried-out own research it is possible to conclude that at glaucomas the infringement of drainage function and increase of intraocular pressure is in many respects caused by high concentration of fibronectin and, partially, insulin-

As it was noted above, the content of PgЕ2 considerably increases in aqueous humour of

There is scanty literature about the synthesis of prostaglandins in eye membranes. Local synthesis of prostaglandins is found out only in cells of crystalline lens that was proved by research of O. Nishi et al. (1992) in model experiments *in vitro*: at cataract the extracted lens in the course of operation was located on incubation medium. With the increase of incubation terms the content of prostaglandins Е<sup>2</sup> in the incubation environment considerably increased. At the same time, in a number of eye membranes, the ciliary body, sclera and the trabecular meshwork of an angle of the anterior chamber of an eye receptors to prostaglandins Е2 were

It is not excluded that the high content of PgЕ<sup>2</sup> in aqueous humour is fraught with an increase of intraocular pressure at glaucomatous patients, as according to [*Podos S.M. et al., 1972 a; b; Podos S.M., 1976 a; b; c*], PgЕ2 takes an active part in maintenance of drainage function of an

It is known that ionic balance in liquid media of an organism (blood, spinal, gingival, synovial and intraocular liquids) is a necessary condition for maintenance of the osmotic pressure.

The anterior and posterior chambers of an eye are main depots; water makes about 93% and a very insignificant share make proteins. It is considered established that the delay of outflow of aqueous humour or its intensive more "production" promotes considerable elevation of

Thus, one of the factors leading to increase of intraocular pressure at glaucomas is the increase

It is considered to be established long ago that at anterior open-angle glaucoma in aqueous humour there are serious impairments in its ionic structure that was shown by disorders in functioning of sodium ‒ potassium pomp, with the superfluous accumulation of sodium ions. In our research as demonstrated by the results of ion-selective analysis, at primary open-angle glaucomas and pseudoexfoliative glaucomas rather high indices of ions of sodium and calcium and low indices of potassium were determined in aqueous humour, as compared with the

indices defined in aqueous humour of patients with senile not complicated cataracts.

of an eye that, in its turn, is fraught with the increase of intraocular pressure.

The similar imbalance, being shown as superfluous accumulation of sodium and calcium in aqueous humour, complicates normal outflow of aqueous humour from the anterior chamber

Without considering the questions connected with mechanisms of shifts found by us regarding electrolytes content in aqueous humour (that was not an actual problem of the present research), nevertheless we consider expedient to discuss some aspects connected with the fact

patients with primary open-angle glaucomas and pseudoexfoliative glaucomas.

like growth factor-1 in the intraocular liquid.

found [*Toris C.B. et al., 2008*].

92 Glaucoma - Basic and Clinical Aspects

pressure inside an eye.

of osmolarity of intraocular liquid.

eye.

Firstly, the increase of Na+ and Ca++ levels observed by us in aqueous humour should be considered from positions of the broken ionic balance between specific membranes of an eye and intraocular liquid, and not as a result of the general disorder of electrolytes composition in blood of experimental animals, because the level of studied electrolytes in blood serum was within the limits of control values.

Secondly, the high level of a cortisol found by us in aqueous humour can serve one of possible causes of infringement of the ionic balance. This assumption appears very reasonable, as it is known that high concentrations of cortisol in separate membranes of an eye lead to ionic imbalance in connection with enhanced inflow of ions of sodium in aqueous humour that results in an increase of intraocular pressure.

Thirdly, it is not excluded that realization of hormonal and cytokine-dependent processes conditioned by regional shifts in the content of cortisol, prolactin, fibronectin, insulin-like growth factor-1 at cataracts proceeding on the background of primary open-angle glaucoma and pseudoexfoliative glaucoma, is caused by activation of calcium-dependent reactions in secretory cells of eye membranes.

It is considered established that the pseudoexfoliative syndrome represents itself as a provok‐ ing factor for development of the open-angle glaucoma, the course of which has a progressing character and is characterized by high resistance to carried-out medicamentous therapy and an unfavourable forecast [*Prince A.J, Ritch R., 1986; Streeten B.W. et al., 1990; Tarkkanen A. et al., 2002; Takhchidi K.P. et al., 2010*].

One of severe complications at development of a pseudoexfoliative syndrome is cataract as well [*Küchle M. et al., 1997; Puska P., Tarkkanen A., 2001*].

The impairment of immunological tolerance (of immunological privileges of an eye – ACAID) acts as an initiating factor for development of pseudoexfoliative syndrome [*Takhchidi K.P. et. al., 2010*].

It is not excluded that in pathogenesis of pseudoexfoliative syndrome emergence are also involved the local hormonal-mediatory mechanisms connected not with the operational intervention, but rather with infringement of processes of synthesis and secretion of such cytokines as TgFβ-2, IGF-1 and, first of all, fibronectin in cornea, ciliary body and trabecular meshwork of synthesis.

At a pseudoexfoliative syndrome essential physical and chemical changes occur in aqueous humour: the concentration of proteins considerably raises, including fibronectin as well [*Takhchidi K.P. et al., 2010*]. At the same time, shifts found by us in aqueous humour of patients with cataract on the background of pseudoexfoliative glaucoma, in many respects depend on the character of disease course: not so much of cataract, as glaucoma and the pseudoexfoliative syndrome. It is not excluded that in this studied group the high level of fibronectin in aqueous humour in many respects depends on features of pseudoexfoliative syndrome development.

On the basis of the analysis of literary data, it is possible to come to conclusion, according to which TGFβ-2 developed in eye membranes plays far not the last role in pathogenesis of primary open-angle glaucoma, including pseudoexfoliative glaucoma as well. So, at glaucomas of TGFβ-2 stimulates synthesis of such cytokines as insulin-like growth factor-1 and fibronectin in cornea, ciliary body and a trabecular meshwork of an angle of the anterior chamber of an eye. Their high levels found by us in aqueous humour testify to possible violation of drainage function of the trabecular meshwork that is fraught with an increase of intraocular pressure.

drainage function and development of a symptom complex that is characteristic for primary

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95

**Scheme 1.** The role of trabecular meshwork cells of the anterior chamber angle of an eye in mechanisms of fibronectin-de‐ pendent drainage function impairment and the increase of intraocular pressure at anterior open-angle glaucoma

open-angle and pseudoexfoliative glaucoma.

In conclusion, in the form of generalized schemes 1 and 2 the possible pathogenetic links engaged in the induction and a course of primary open-angle glaucoma, including pseudoex‐ foliative glaucoma as well, are presented to attention of ophthalmologists. The specific subject matter is regional disorder that is fraught with impairment of secretory activity of the poly‐ potent cells localized in various eye membranes, which besides the main functions produce a number of biologically active substances of the cytokine, hormonal and mediatory nature.

At anterior open-angle glaucoma (see schemes 1 and 2) the synthesis of fibronectin in cells of the trabecular meshwork is considerably activated which is caused by the stimulating influence of fibroblasts transforming growth factor (TGFβ-2). Realization of this effect, to a certain extent, is caused by blocking of inhibitory effect of a bone morfogenic protein (BMP-4) towards the activity of TGFβ-2 due to which the stimulating effect of the latter on processes of fibronectin intra-cellular synthesis is realized. It is not excluded that at the same time there occurs blocking of inhibitory effect of TGFβ-1 on domain of heparin (Hep-2) responsible for synthesis of fibronectin in a cell.

Further, as a result of fibronectin "hyper production", there is a deposition of fibronectin in extracellular matrix (EM) owing to which, as a result of drainage function impairment in trabecular meshwork, there proceeds an increase of intraocular pressure.

It is not excluded that in the conditions of physiological activity of trabecular meshwork cells the processes of intra-cellular synthesis of fibronectin are regulated according to cytokine mechanisms in realization of which, on the one hand, TGFβ-2 serves as a stimulating factor, on the other hand, this stimulating effect is adjusted due to gremin (G) and BMP-4 produced in trabecular meshwork cells. It is precisely the coordinated activity of aforementioned cytokines, TGFβ-2, G and BMP-4, that strictly supervises the balanced synthesis of fibronectin cells by trabecular network cells in the conditions of norm.

The specified Scheme 1 was constructed by us upon the analysis of the modern data concerning a role fibronectin, which is produced in keratocytes and cells of a trabecular meshwork, in violation of the drainage function of an eye at glaucomas and complicated cataracts [*Gonzales J.M. et al., 1998; Fleenor D. et al., 2006; Wordinger R.J. et al., 2007; Stefan C. et al., 2008; Zilfyan A., 2009; 2012; Hindman H.B. et al., 2010*].

In addition, due to analysis of the modern scientific data in the aspect of our own research findings we propose a summary scheme (Scheme 2) that presents the role of *in situ* produced biologically active compounds, which under conditions of disorders in synchronous activity of secretory cells localized in various membranes of the eye might bring to impairment of the drainage function and development of a symptom complex that is characteristic for primary open-angle and pseudoexfoliative glaucoma.

On the basis of the analysis of literary data, it is possible to come to conclusion, according to which TGFβ-2 developed in eye membranes plays far not the last role in pathogenesis of primary open-angle glaucoma, including pseudoexfoliative glaucoma as well. So, at glaucomas of TGFβ-2 stimulates synthesis of such cytokines as insulin-like growth factor-1 and fibronectin in cornea, ciliary body and a trabecular meshwork of an angle of the anterior chamber of an eye. Their high levels found by us in aqueous humour testify to possible violation of drainage function of the trabecular meshwork that is fraught with an increase of intraocular pressure.

In conclusion, in the form of generalized schemes 1 and 2 the possible pathogenetic links engaged in the induction and a course of primary open-angle glaucoma, including pseudoex‐ foliative glaucoma as well, are presented to attention of ophthalmologists. The specific subject matter is regional disorder that is fraught with impairment of secretory activity of the poly‐ potent cells localized in various eye membranes, which besides the main functions produce a number of biologically active substances of the cytokine, hormonal and mediatory nature.

At anterior open-angle glaucoma (see schemes 1 and 2) the synthesis of fibronectin in cells of the trabecular meshwork is considerably activated which is caused by the stimulating influence of fibroblasts transforming growth factor (TGFβ-2). Realization of this effect, to a certain extent, is caused by blocking of inhibitory effect of a bone morfogenic protein (BMP-4) towards the activity of TGFβ-2 due to which the stimulating effect of the latter on processes of fibronectin intra-cellular synthesis is realized. It is not excluded that at the same time there occurs blocking of inhibitory effect of TGFβ-1 on domain of heparin (Hep-2) responsible for

Further, as a result of fibronectin "hyper production", there is a deposition of fibronectin in extracellular matrix (EM) owing to which, as a result of drainage function impairment in

It is not excluded that in the conditions of physiological activity of trabecular meshwork cells the processes of intra-cellular synthesis of fibronectin are regulated according to cytokine mechanisms in realization of which, on the one hand, TGFβ-2 serves as a stimulating factor, on the other hand, this stimulating effect is adjusted due to gremin (G) and BMP-4 produced in trabecular meshwork cells. It is precisely the coordinated activity of aforementioned cytokines, TGFβ-2, G and BMP-4, that strictly supervises the balanced synthesis of fibronectin cells by

The specified Scheme 1 was constructed by us upon the analysis of the modern data concerning a role fibronectin, which is produced in keratocytes and cells of a trabecular meshwork, in violation of the drainage function of an eye at glaucomas and complicated cataracts [*Gonzales J.M. et al., 1998; Fleenor D. et al., 2006; Wordinger R.J. et al., 2007; Stefan C. et al., 2008; Zilfyan A.,*

In addition, due to analysis of the modern scientific data in the aspect of our own research findings we propose a summary scheme (Scheme 2) that presents the role of *in situ* produced biologically active compounds, which under conditions of disorders in synchronous activity of secretory cells localized in various membranes of the eye might bring to impairment of the

trabecular meshwork, there proceeds an increase of intraocular pressure.

trabecular network cells in the conditions of norm.

*2009; 2012; Hindman H.B. et al., 2010*].

synthesis of fibronectin in a cell.

94 Glaucoma - Basic and Clinical Aspects

**Scheme 1.** The role of trabecular meshwork cells of the anterior chamber angle of an eye in mechanisms of fibronectin-de‐ pendent drainage function impairment and the increase of intraocular pressure at anterior open-angle glaucoma

destructive processes, mechanisms of which are not sufficiently studied until present. In the given scheme we consider only 1 point of application that is affected by the influence of all the above mentioned factors: as a "target" here serves the trabecular meshwork of the anterior chamber of an eye with impaired drainage function that eventually rings to an increase of intraocular pressure. As evident from Scheme 2, in case of anterior open-angle glaucoma the regional TGFβ-2 dependent mechanisms are engaged, being conditioned by its stimulating influence to secretory cells of some eye membranes: in the aspect of their "excessive" synthesis of fibronectin and IGFβ-2, which cumulate both in stroma of the trabecular meshwork and in the aqueous humour finally resulting in block of drainage system and an increase of intraocular pressure. The hyperproduction of PgE2 in secretory cells of trabecular meshwork, sclera and, probably, the lens, also brings forth impairment of the drainage function. In impairment of drainage network functions a definite role is also devoted to *in situ* produced cortisol and processes resulting in disorders of ionic balance between the membranes and liquid media of an eye (first of all: between the cells of the ciliary body, cornea, trabecular meshwork and the aqueous humour). In the mechanism of impaired ionic balance that at the primary open-angle glaucoma is characterized by excessive accumulation of sodium ions in aqueous humour a certain part belongs also to cortisol produced in eye membranes. In cases of pseudoexfoliative glaucoma deposition of pseudoexfoliative matter in the anterior segment of an eye might cause

Modern Aspects of Glaucoma Pathogenesis Local Factors for Development of Primary Open-Angle Glaucoma…

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blocking of the drainage system.

Address all correspondence to: namj@ysmu.am, zilf.art@mail.ru

2 "Shengavit" Medical Center, Yerevan, Armenia

1 Scientific-Research Center, Yerevan State Medical University, Yerevan, Armenia

[1] Abrahamian, A, Xi, M, Donnelly, J, & Rockey, J. Effect of interferon-gamma on the expression of transforming growth factor-beta by human corneal fibroblasts: role in

[2] Banh, A, Deschamps, P. A, Gauldie, J, Overbeek, P. A, Sivak, J. G, & West-mays, J. A. Lens-specific expression of TGF-beta induces anterior subcapsular cataract formation in the absence of Smad3. Invest. Ophthalmol. Vis. Sci. (2006). Aug; , 47(8), 3450-3460.

corneal immunoseclusion. J. Interferon Cytokine Res. (1995). , 15(4), 323-330.

**Author details**

A.A. Zilfyan1,2\*

**References**

**Scheme 2.** The role of mediators and hormones in mechanisms of intraocular pressure increase at complicated cata‐ racts: cataracts on the background of primary open-angle glaucoma and pseudoexfoliative glaucoma

As obvious from Scheme 2, regional factors engaged in mechanisms of drainage function impairment and intraocular pressure increase might be conditionally divided into 2 categories. Secretory processes associated with dysfunction of cornea and trabecular meshwork cells (in the aspect of their targeted synthesis of TGFβ-2 should be related to category 1. Category 2 should embrace hormonal disorders, impairment of the regional ionic homeostasis and destructive processes, mechanisms of which are not sufficiently studied until present. In the given scheme we consider only 1 point of application that is affected by the influence of all the above mentioned factors: as a "target" here serves the trabecular meshwork of the anterior chamber of an eye with impaired drainage function that eventually rings to an increase of intraocular pressure. As evident from Scheme 2, in case of anterior open-angle glaucoma the regional TGFβ-2 dependent mechanisms are engaged, being conditioned by its stimulating influence to secretory cells of some eye membranes: in the aspect of their "excessive" synthesis of fibronectin and IGFβ-2, which cumulate both in stroma of the trabecular meshwork and in the aqueous humour finally resulting in block of drainage system and an increase of intraocular pressure. The hyperproduction of PgE2 in secretory cells of trabecular meshwork, sclera and, probably, the lens, also brings forth impairment of the drainage function. In impairment of drainage network functions a definite role is also devoted to *in situ* produced cortisol and processes resulting in disorders of ionic balance between the membranes and liquid media of an eye (first of all: between the cells of the ciliary body, cornea, trabecular meshwork and the aqueous humour). In the mechanism of impaired ionic balance that at the primary open-angle glaucoma is characterized by excessive accumulation of sodium ions in aqueous humour a certain part belongs also to cortisol produced in eye membranes. In cases of pseudoexfoliative glaucoma deposition of pseudoexfoliative matter in the anterior segment of an eye might cause blocking of the drainage system.
