Progress in Retinal and Eye Research 39 (2014) 107e110
Contents lists available at ScienceDirect
Progress in Retinal and Eye Research journal homepage: www.elsevier.com/locate/prer
The role of low intracranial pressure in the development of glaucoma in patients with Alzheimer’s disease Keywords: Alzheimer’s disease Cerebrospinal fluid pressure Glaucoma Intracranial pressure
October 22, 2013 Dear Editor, We read with great interest the paper by Janssen et al. (2013) entitled ‘The vast complexity of primary open angle glaucoma: Disease genes, risks, molecular mechanisms and pathobiology.’ The authors deserve appreciation for their very informative review article. However, we wish to make a comment concerning their discussion of the potential role of intracranial pressure (ICP) in Alzheimer’s disease (AD) and glaucoma. In the last section of their paper, Janssen and colleagues discuss the potential relation between primary open angle glaucoma (POAG) and AD. As the authors mention, several studies have found an increase in the occurrence of glaucoma in AD patients. The authors state: “In our view, POAG damage could be caused by the net pressure over the optic disk, involving both the aqueous humor pressure of the eye and cerebrospinal fluid (CSF) pressure of the brain, as described above. Also, CSF pressure changes have been described in AD (Silverberg et al., 2006). Could these pressure changes underlie a relationship between POAG and AD, and at the same time explain the apparently conflicting association studies?” Further, the authors state: “We hypothesize that there is a strong association between normal pressure glaucoma and late AD, since both disease stages, following the ‘net pressure on the optic disk hypothesis’, are characterized by one single disease mechanism: an abnormally low ICP.” Janssen et al. (2013) thus hypothesize that low ICP may play a role in the association between glaucoma and AD. We fully agree with the authors since our group has previously presented this hypothesis for the first time (Wostyn et al., 2008, 2009a). In two of our earlier manuscripts published in 2008 (Wostyn et al., 2008) and 2009 (Wostyn et al., 2009a), we proposed low ICP occurring in AD as a factor leading to increased risk of glaucoma. Evidence for this hypothesis was gained from CSF pressure measurement studies in AD patients and patients with glaucoma. The finding of a high occurrence of reduced CSF pressure among patients with AD (Silverberg et al., 2006; Wostyn et al., 2009b) could be linked to the high rate of reported comorbidity between AD and glaucoma (Bayer et al., 2002; Tamura et al., 2006), since it has been shown 1350-9462/$ e see front matter Ó 2013 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.preteyeres.2013.12.002
that CSF pressure is lower in patients with glaucoma (Berdahl et al., 2008a, 2008b; Ren et al., 2010). This could result in an abnormally high trans-lamina cribrosa pressure difference and lead to glaucomatous damage. Given this previously advanced hypothesis, it was a great surprise when Janssen et al. (2013) recently hypothesized about the potential role of low ICP in glaucoma and AD without citing our earlier work (Wostyn et al., 2008, 2009a) or making clear the relevant precedents. The authors did cite one of our papers, one largely focused on the high occurrence rate of glaucoma among patients with normal pressure hydrocephalus (Wostyn et al., 2010), but this paper has no direct relevance to the above hypothesis. Sincerely yours, Peter Wostyn, MD Veva De Groot, MD, PhD Debby Van Dam, PhD Kurt Audenaert, MD, PhD Peter Paul De Deyn, MD, PhD References Bayer, A.U., Ferrari, F., Erb, C., 2002. High occurrence rate of glaucoma among patients with Alzheimer’s disease. Eur. Neurol. 47, 165e168. Berdahl, J.P., Allingham, R.R., Johnson, D.H., 2008a. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology 115, 763e 768. Berdahl, J.P., Fautsch, M.P., Stinnett, S.S., Allingham, R.R., 2008b. Intracranial pressure in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension: a case-control study. Investig. Ophthalmol. Vis. Sci. 49, 5412e 5418. Janssen, S.F., Gorgels, T.G., Ramdas, W.D., Klaver, C.C., van Duijn, C.M., Jansonius, N.M., Bergen, A.A., 2013. The vast complexity of primary open angle glaucoma: disease genes, risks, molecular mechanisms and pathobiology. Prog. Retin. Eye Res. 37, 31e67. Ren, R., Jonas, J.B., Tian, G., Zhen, Y., Ma, K., Li, S., Wang, H., Li, B., Zhang, X., Wang, N., 2010. Cerebrospinal fluid pressure in glaucoma: a prospective study. Ophthalmology 117, 259e266. Silverberg, G., Mayo, M., Saul, T., Fellmann, J., McGuire, D., 2006. Elevated cerebrospinal fluid pressure in patients with Alzheimer’s disease. Cerebrospinal Fluid Res. 3, 7. Tamura, H., Kawakami, H., Kanamoto, T., Kato, T., Yokoyama, T., Sasaki, K., Izumi, Y., Matsumoto, M., Mishima, H.K., 2006. High frequency of openangle glaucoma in Japanese patients with Alzheimer’s disease. J. Neurol. Sci. 246, 79e83. Wostyn, P., Audenaert, K., De Deyn, P.P., 2008. An abnormal high trans-lamina cribrosa pressure difference: a missing link between Alzheimer’s disease and glaucoma? Clin. Neurol. Neurosurg. 110, 753e754. Wostyn, P., Audenaert, K., De Deyn, P.P., 2009a. Alzheimer’s disease and glaucoma: is there a causal relationship? Br. J. Ophthalmol. 93, 1557e1559. Wostyn, P., Audenaert, K., De Deyn, P.P., 2009b. More advanced Alzheimer’s disease may be associated with a decrease in cerebrospinal fluid pressure. Cerebrospinal Fluid Res. 6, 14. Wostyn, P., Audenaert, K., De Deyn, P.P., 2010. High occurrence rate of glaucoma among patients with normal pressure hydrocephalus. J. Glaucoma 19, 225e 226.
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Peter Wostyn* Department of Psychiatry, PC Sint-Amandus, Reigerlostraat 10, 8730 Beernem, Belgium Veva De Groot Department of Ophthalmology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Antwerp, Belgium E-mail address: [email protected]. Debby Van Dam Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Department of Biomedical Sciences, Universiteitsplein 1, 2610 Antwerp, Belgium E-mail address: [email protected].
Peter Paul De Deyn Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Department of Biomedical Sciences, Universiteitsplein 1, 2610 Antwerp, Belgium Department of Neurology and Memory Clinic, Middelheim General Hospital (ZNA), Lindendreef 1, 2020 Antwerp, Belgium Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands E-mail address: [email protected]. * Corresponding
author. Tel.: þ32 472713719; fax: þ32 50 819720. E-mail address: [email protected] (P. Wostyn).
Kurt Audenaert Department of Psychiatry, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium E-mail address: [email protected].
Available online 4 January 2014
Alzheimer’s disease and glaucoma e Reply October 31, 2013 Dear Editor, We thank Wostyn and coworkers for their constructive comments on our article: The vast complexity of primary open angle glaucoma: disease genes, risks, molecular mechanisms, pathobiology (Janssen et al., 2013). We felt that a full discussion on the relationship between Primary Open Angle Glaucoma (POAG) and Alzheimer’s disease (AD), with at least 85 articles in Pubmed, was outside the scope of our glaucoma review. Nonetheless, we wished to add a small AD paragraph to this POAG review in order to make readers aware of (1) the nature of the possible relationship between POAG and AD, (2) possible confounding factors in (genetic) epidemiological studies related to these two disease entities, and (3) the fact that the four functional molecular networks we constructed for POAG probably have some relevance for molecular modeling of AD as well. To illustrate the last point further, we show in Fig. 1 the four functional molecular POAG networks we constructed previously (Figs. 7e10 in Janssen et al., 2013), but now annotated for genes known to be involved in AD. It was this data, together with the literature, which guided our thoughts about the relation(s) between glaucoma and AD, and the hypothesis mentioned. Decades ago, it was shown in animal studies that the morphology of the optic disc is subject to both the intraocular (IOP) and intracranial pressure (ICP) (Maumenee, 1983; Jonas et al., 1991; Morgan et al., 1995). Changes in the morphology of the lamina cribrosa were correlated with disturbed axonal cell transport and ganglion cell death (Minckler et al., 1976; Quigley et al., 1979). Subsequently, patient studies also pointed towards a relationship between glaucoma and a low(er) ICP (e.g. Jonas et al.,
2003; Berdahl et al., 2008a, 2008b; Ren et al., 2010; Wang et al., 2012). Meanwhile, Silverberg et al. (2006) discovered that ICP disturbances may also occur in patients with AD. Combining the results from these studies, Wostyn and coworkers posed their hypothesis on decreased ICP, linking POAG and AD (Wostyn et al., 2008, 2009). From a molecular point of view, genes involved in both POAG and AD may play a role in the IOP and ICP dynamics or in other functionalities which possibly links the pathobiology of POAG and AD (Copin et al., 2002; Fourgeux et al., 2009; Liu and Tian, 2011). We had no intention not to acknowledge the original contribution(s) of Wostyn and colleagues on this subject in the literature (Wostyn et al., 2008, 2009), nor the contribution of many others. We now realize that the sentence “We hypothesize.” in the last paragraph may come across as if we pose this idea for the first time. We regret this impression. We do hope that bundling of all available knowledge, including molecular, in vitro and in vivo functional studies, clinical and epidemiological studies will lead to further understanding of the pathobiology of glaucoma, both inside and outside the eye. Sincerely yours, Sarah F. Janssen, MD Theo G.M.F. Gorgels, PhD Wishal D. Ramdas, MD, PhD Caroline C.W. Klaver, MD, PhD Cornelia M. van Duijn, PhD Nomdo M. Jansonius, MD, PhD Arthur A.B. Bergen, PhD
P. Wostyn et al. / Progress in Retinal and Eye Research 39 (2014) 107e110
109
Fig. 1. Functional molecular networks of (candidate) POAG disease genes annotated for genes involved in Alzheimer’s disease. This figure presents the four functional molecular networks we deduced from 65 selected candidate POAG disease genes (Janssen et al., 2013). We now annotated these functional molecular networks in Ingenuity with candidate genes previously implicated in Alzheimer’s disease in the literature. Obviously, there appears to be a major overlap between the molecular background of POAG and Alzheimer’s disease. Orange genes represent genes with a genetic association with Alzheimer’s disease (e.g. mutations in this gene increases the risk for Alzheimer’s disease), whereas green symbols represent a functional link with Alzheimer’s disease (e.g. up- or downregulation in tissues in Alzheimer’s disease). Abbreviations: POAG ¼ primary open-angle glaucoma.
References Berdahl, J.P., Allingham, R.R., Johnson, D.H., 2008a. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology 115, 763e768. Berdahl, J.P., Fautsch, M.P., Stinnett, S.S., Allingham, R.R., 2008b. Intracranial pressure in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension: a case-control study. Investig. Ophthalmol. Vis. Sci. 49, 5412e5418. Copin, B., Brézin, A.P., Valtot, F., Dascotte, J.C., Béchetoille, A., Garchon, H.J., 2002. Am. J. Hum. Genet. 70, 1575e1581. Fourgeux, C., Martine, L., Björkhem, I., Diczfalusy, U., Joffre, C., Acar, N., CreuzotGarcher, C., Bron, A., Bretillon, L., 2009. Primary open-angle glaucoma: association with cholesterol 24S-hydroxylase (CYP46A1) gene polymorphism and plasma 24-hydroxylcholesterol levels. Investig. Ophthalmol. Vis. Sci. 50, 5712e5717. Janssen, S.F., Gorgels, T.G., Ramdas, W.D., Klaver, C.C., van Duijn, C.M., Jansonius, N.M., Bergen, A.A., 2013. The vast complexity of primary open angle glaucoma: disease genes, risks, molecular mechanisms and pathobiology. Prog. Retin. Eye Res. 37, 31e67. Jonas, J.B., Mardin, C.Y., Schlötzer-Schrehardt, U., Naumann, G.O., 1991. Morphology of the human lamina cribrosa surface. Investig. Ophthalmol. Vis. Sci. 32, 401e 405. Jonas, J.B., Berenshtein, E., Holbach, L., 2003. Anatomic relationship between lamina cribrosa, intraocular space, and cerebrospinal fluid space. Investig. Ophthalmol. Vis. Sci. 44, 5189e5195.
Liu, Y.H., Tian, T., 2011. Hypothesis of optineurin as a new common risk factor in normal-tension glaucoma and Alzheimer’s disease. Med. Hypothesis 77, 591e 592. Maumenee, A.E., 1983. Causes of optic nerve damage in glaucoma. Robert N. Shaffer lecture. Ophthalmology 90, 741e752. Minckler, D.S., Tso, M.O., Zimmerman, L.E., 1976. A light microscopic, autoradiographic study of axoplasmic transport in the optic nerve head during ocular hypotony, increased intraocular pressure, and papilledema. Am. J. Ophthalmol. 82, 741e757. Morgan, W.H., Yu, D.Y., Cooper, R.L., Alder, V.A., Cringle, S.J., Constable, I.J., 1995. The influence of cerebrospinal fluid pressure on the lamina cribrosa tissue pressure gradient. Investig. Ophthalmol. Vis. Sci. 36, 1163e1172. Quigley, H.A., Guy, J., Anderson, D.R., 1979. Blockade of rapid axonal transport. Effect of intraocular pressure elevation in primate optic nerve. Arch. Ophthalmol. 97, 525e531. Ren, R., Jonas, J.B., Tian, G., Zhen, Y., Ma, K., Li, S., Wang, H., Li, B., Zhang, X., Wang, N., 2010. Cerebrospinal fluid pressure in glaucoma: a prospective study. Ophthalmology 117, 259e266. Silverberg, G., Mayo, M., Saul, T., Fellmann, J., McGuire, D., 2006. Elevated cerebrospinal fluid pressure in patients with Alzheimer’s disease. Cerebrospinal Fluid Res. 31, 3e7. Wang, N., Xie, X., Yang, D., Xian, J., Li, Y., Ren, R., Peng, X., Jonas, J.B., Weinreb, R.N., 2012. Orbital cerebrospinal fluid space in glaucoma: the Beijing intracranial and intraocular pressure (iCOP) study. Ophthalmology 119, 2065e2073.
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Wostyn, P., Audenaert, K., De Deyn, P.P., 2008. An abnormal high trans-lamina cribrosa pressure difference: a missing link between Alzheimer’s disease and glaucoma? Clin. Neurol. Neurosurg. 110, 753e754. Wostyn, P., Audenaert, K., De Deyn, P.P., 2009. Alzheimer’s disease and glaucoma: is there a causal relationship? Br. J. Ophthalmol. 93, 1557e1559.
Sarah F. Janssen, Theo G.M.F. Gorgels Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands E-mail addresses: [email protected] (S.F. Janssen), [email protected] (T.G.M.F. Gorgels). Wishal D. Ramdas, Caroline C.W. Klaver Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands Department of Ophthalmology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands E-mail addresses: [email protected] (W.D. Ramdas), [email protected] (C.C.W. Klaver). Cornelia M. van Duijn Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands E-mail address: [email protected].
Nomdo M. Jansonius Department of Ophthalmology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands E-mail address: [email protected]. Arthur A.B. Bergen* Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands * Corresponding author. Department of Ophthalmogenetics, The Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands. Tel.: þ31 205666101; fax: þ31 205666121. E-mail address: [email protected] (A.A.B. Bergen). Available online 4 January 2014
Contents lists available at ScienceDirect
Progress in Retinal and Eye Research journal homepage: www.elsevier.com/locate/prer
The role of low intracranial pressure in the development of glaucoma in patients with Alzheimer’s disease Keywords: Alzheimer’s disease Cerebrospinal fluid pressure Glaucoma Intracranial pressure
October 22, 2013 Dear Editor, We read with great interest the paper by Janssen et al. (2013) entitled ‘The vast complexity of primary open angle glaucoma: Disease genes, risks, molecular mechanisms and pathobiology.’ The authors deserve appreciation for their very informative review article. However, we wish to make a comment concerning their discussion of the potential role of intracranial pressure (ICP) in Alzheimer’s disease (AD) and glaucoma. In the last section of their paper, Janssen and colleagues discuss the potential relation between primary open angle glaucoma (POAG) and AD. As the authors mention, several studies have found an increase in the occurrence of glaucoma in AD patients. The authors state: “In our view, POAG damage could be caused by the net pressure over the optic disk, involving both the aqueous humor pressure of the eye and cerebrospinal fluid (CSF) pressure of the brain, as described above. Also, CSF pressure changes have been described in AD (Silverberg et al., 2006). Could these pressure changes underlie a relationship between POAG and AD, and at the same time explain the apparently conflicting association studies?” Further, the authors state: “We hypothesize that there is a strong association between normal pressure glaucoma and late AD, since both disease stages, following the ‘net pressure on the optic disk hypothesis’, are characterized by one single disease mechanism: an abnormally low ICP.” Janssen et al. (2013) thus hypothesize that low ICP may play a role in the association between glaucoma and AD. We fully agree with the authors since our group has previously presented this hypothesis for the first time (Wostyn et al., 2008, 2009a). In two of our earlier manuscripts published in 2008 (Wostyn et al., 2008) and 2009 (Wostyn et al., 2009a), we proposed low ICP occurring in AD as a factor leading to increased risk of glaucoma. Evidence for this hypothesis was gained from CSF pressure measurement studies in AD patients and patients with glaucoma. The finding of a high occurrence of reduced CSF pressure among patients with AD (Silverberg et al., 2006; Wostyn et al., 2009b) could be linked to the high rate of reported comorbidity between AD and glaucoma (Bayer et al., 2002; Tamura et al., 2006), since it has been shown 1350-9462/$ e see front matter Ó 2013 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.preteyeres.2013.12.002
that CSF pressure is lower in patients with glaucoma (Berdahl et al., 2008a, 2008b; Ren et al., 2010). This could result in an abnormally high trans-lamina cribrosa pressure difference and lead to glaucomatous damage. Given this previously advanced hypothesis, it was a great surprise when Janssen et al. (2013) recently hypothesized about the potential role of low ICP in glaucoma and AD without citing our earlier work (Wostyn et al., 2008, 2009a) or making clear the relevant precedents. The authors did cite one of our papers, one largely focused on the high occurrence rate of glaucoma among patients with normal pressure hydrocephalus (Wostyn et al., 2010), but this paper has no direct relevance to the above hypothesis. Sincerely yours, Peter Wostyn, MD Veva De Groot, MD, PhD Debby Van Dam, PhD Kurt Audenaert, MD, PhD Peter Paul De Deyn, MD, PhD References Bayer, A.U., Ferrari, F., Erb, C., 2002. High occurrence rate of glaucoma among patients with Alzheimer’s disease. Eur. Neurol. 47, 165e168. Berdahl, J.P., Allingham, R.R., Johnson, D.H., 2008a. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology 115, 763e 768. Berdahl, J.P., Fautsch, M.P., Stinnett, S.S., Allingham, R.R., 2008b. Intracranial pressure in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension: a case-control study. Investig. Ophthalmol. Vis. Sci. 49, 5412e 5418. Janssen, S.F., Gorgels, T.G., Ramdas, W.D., Klaver, C.C., van Duijn, C.M., Jansonius, N.M., Bergen, A.A., 2013. The vast complexity of primary open angle glaucoma: disease genes, risks, molecular mechanisms and pathobiology. Prog. Retin. Eye Res. 37, 31e67. Ren, R., Jonas, J.B., Tian, G., Zhen, Y., Ma, K., Li, S., Wang, H., Li, B., Zhang, X., Wang, N., 2010. Cerebrospinal fluid pressure in glaucoma: a prospective study. Ophthalmology 117, 259e266. Silverberg, G., Mayo, M., Saul, T., Fellmann, J., McGuire, D., 2006. Elevated cerebrospinal fluid pressure in patients with Alzheimer’s disease. Cerebrospinal Fluid Res. 3, 7. Tamura, H., Kawakami, H., Kanamoto, T., Kato, T., Yokoyama, T., Sasaki, K., Izumi, Y., Matsumoto, M., Mishima, H.K., 2006. High frequency of openangle glaucoma in Japanese patients with Alzheimer’s disease. J. Neurol. Sci. 246, 79e83. Wostyn, P., Audenaert, K., De Deyn, P.P., 2008. An abnormal high trans-lamina cribrosa pressure difference: a missing link between Alzheimer’s disease and glaucoma? Clin. Neurol. Neurosurg. 110, 753e754. Wostyn, P., Audenaert, K., De Deyn, P.P., 2009a. Alzheimer’s disease and glaucoma: is there a causal relationship? Br. J. Ophthalmol. 93, 1557e1559. Wostyn, P., Audenaert, K., De Deyn, P.P., 2009b. More advanced Alzheimer’s disease may be associated with a decrease in cerebrospinal fluid pressure. Cerebrospinal Fluid Res. 6, 14. Wostyn, P., Audenaert, K., De Deyn, P.P., 2010. High occurrence rate of glaucoma among patients with normal pressure hydrocephalus. J. Glaucoma 19, 225e 226.
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Peter Wostyn* Department of Psychiatry, PC Sint-Amandus, Reigerlostraat 10, 8730 Beernem, Belgium Veva De Groot Department of Ophthalmology, Antwerp University Hospital, Wilrijkstraat 10, 2650 Antwerp, Belgium E-mail address: [email protected]. Debby Van Dam Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Department of Biomedical Sciences, Universiteitsplein 1, 2610 Antwerp, Belgium E-mail address: [email protected].
Peter Paul De Deyn Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Department of Biomedical Sciences, Universiteitsplein 1, 2610 Antwerp, Belgium Department of Neurology and Memory Clinic, Middelheim General Hospital (ZNA), Lindendreef 1, 2020 Antwerp, Belgium Department of Neurology and Alzheimer Research Center, University of Groningen and University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands E-mail address: [email protected]. * Corresponding
author. Tel.: þ32 472713719; fax: þ32 50 819720. E-mail address: [email protected] (P. Wostyn).
Kurt Audenaert Department of Psychiatry, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium E-mail address: [email protected].
Available online 4 January 2014
Alzheimer’s disease and glaucoma e Reply October 31, 2013 Dear Editor, We thank Wostyn and coworkers for their constructive comments on our article: The vast complexity of primary open angle glaucoma: disease genes, risks, molecular mechanisms, pathobiology (Janssen et al., 2013). We felt that a full discussion on the relationship between Primary Open Angle Glaucoma (POAG) and Alzheimer’s disease (AD), with at least 85 articles in Pubmed, was outside the scope of our glaucoma review. Nonetheless, we wished to add a small AD paragraph to this POAG review in order to make readers aware of (1) the nature of the possible relationship between POAG and AD, (2) possible confounding factors in (genetic) epidemiological studies related to these two disease entities, and (3) the fact that the four functional molecular networks we constructed for POAG probably have some relevance for molecular modeling of AD as well. To illustrate the last point further, we show in Fig. 1 the four functional molecular POAG networks we constructed previously (Figs. 7e10 in Janssen et al., 2013), but now annotated for genes known to be involved in AD. It was this data, together with the literature, which guided our thoughts about the relation(s) between glaucoma and AD, and the hypothesis mentioned. Decades ago, it was shown in animal studies that the morphology of the optic disc is subject to both the intraocular (IOP) and intracranial pressure (ICP) (Maumenee, 1983; Jonas et al., 1991; Morgan et al., 1995). Changes in the morphology of the lamina cribrosa were correlated with disturbed axonal cell transport and ganglion cell death (Minckler et al., 1976; Quigley et al., 1979). Subsequently, patient studies also pointed towards a relationship between glaucoma and a low(er) ICP (e.g. Jonas et al.,
2003; Berdahl et al., 2008a, 2008b; Ren et al., 2010; Wang et al., 2012). Meanwhile, Silverberg et al. (2006) discovered that ICP disturbances may also occur in patients with AD. Combining the results from these studies, Wostyn and coworkers posed their hypothesis on decreased ICP, linking POAG and AD (Wostyn et al., 2008, 2009). From a molecular point of view, genes involved in both POAG and AD may play a role in the IOP and ICP dynamics or in other functionalities which possibly links the pathobiology of POAG and AD (Copin et al., 2002; Fourgeux et al., 2009; Liu and Tian, 2011). We had no intention not to acknowledge the original contribution(s) of Wostyn and colleagues on this subject in the literature (Wostyn et al., 2008, 2009), nor the contribution of many others. We now realize that the sentence “We hypothesize.” in the last paragraph may come across as if we pose this idea for the first time. We regret this impression. We do hope that bundling of all available knowledge, including molecular, in vitro and in vivo functional studies, clinical and epidemiological studies will lead to further understanding of the pathobiology of glaucoma, both inside and outside the eye. Sincerely yours, Sarah F. Janssen, MD Theo G.M.F. Gorgels, PhD Wishal D. Ramdas, MD, PhD Caroline C.W. Klaver, MD, PhD Cornelia M. van Duijn, PhD Nomdo M. Jansonius, MD, PhD Arthur A.B. Bergen, PhD
P. Wostyn et al. / Progress in Retinal and Eye Research 39 (2014) 107e110
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Fig. 1. Functional molecular networks of (candidate) POAG disease genes annotated for genes involved in Alzheimer’s disease. This figure presents the four functional molecular networks we deduced from 65 selected candidate POAG disease genes (Janssen et al., 2013). We now annotated these functional molecular networks in Ingenuity with candidate genes previously implicated in Alzheimer’s disease in the literature. Obviously, there appears to be a major overlap between the molecular background of POAG and Alzheimer’s disease. Orange genes represent genes with a genetic association with Alzheimer’s disease (e.g. mutations in this gene increases the risk for Alzheimer’s disease), whereas green symbols represent a functional link with Alzheimer’s disease (e.g. up- or downregulation in tissues in Alzheimer’s disease). Abbreviations: POAG ¼ primary open-angle glaucoma.
References Berdahl, J.P., Allingham, R.R., Johnson, D.H., 2008a. Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma. Ophthalmology 115, 763e768. Berdahl, J.P., Fautsch, M.P., Stinnett, S.S., Allingham, R.R., 2008b. Intracranial pressure in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension: a case-control study. Investig. Ophthalmol. Vis. Sci. 49, 5412e5418. Copin, B., Brézin, A.P., Valtot, F., Dascotte, J.C., Béchetoille, A., Garchon, H.J., 2002. Am. J. Hum. Genet. 70, 1575e1581. Fourgeux, C., Martine, L., Björkhem, I., Diczfalusy, U., Joffre, C., Acar, N., CreuzotGarcher, C., Bron, A., Bretillon, L., 2009. Primary open-angle glaucoma: association with cholesterol 24S-hydroxylase (CYP46A1) gene polymorphism and plasma 24-hydroxylcholesterol levels. Investig. Ophthalmol. Vis. Sci. 50, 5712e5717. Janssen, S.F., Gorgels, T.G., Ramdas, W.D., Klaver, C.C., van Duijn, C.M., Jansonius, N.M., Bergen, A.A., 2013. The vast complexity of primary open angle glaucoma: disease genes, risks, molecular mechanisms and pathobiology. Prog. Retin. Eye Res. 37, 31e67. Jonas, J.B., Mardin, C.Y., Schlötzer-Schrehardt, U., Naumann, G.O., 1991. Morphology of the human lamina cribrosa surface. Investig. Ophthalmol. Vis. Sci. 32, 401e 405. Jonas, J.B., Berenshtein, E., Holbach, L., 2003. Anatomic relationship between lamina cribrosa, intraocular space, and cerebrospinal fluid space. Investig. Ophthalmol. Vis. Sci. 44, 5189e5195.
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Sarah F. Janssen, Theo G.M.F. Gorgels Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands E-mail addresses: [email protected] (S.F. Janssen), [email protected] (T.G.M.F. Gorgels). Wishal D. Ramdas, Caroline C.W. Klaver Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands Department of Ophthalmology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands E-mail addresses: [email protected] (W.D. Ramdas), [email protected] (C.C.W. Klaver). Cornelia M. van Duijn Department of Epidemiology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands E-mail address: [email protected].
Nomdo M. Jansonius Department of Ophthalmology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands E-mail address: [email protected]. Arthur A.B. Bergen* Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands Department of Ophthalmology, Academic Medical Center, Amsterdam, The Netherlands Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands * Corresponding author. Department of Ophthalmogenetics, The Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The Netherlands. Tel.: þ31 205666101; fax: þ31 205666121. E-mail address: [email protected] (A.A.B. Bergen). Available online 4 January 2014
