Die Schlüsselrolle der Multiomics in Prädiktion, Prävention und personalisierter Behandlung vom Glaukom

Zusammenfassung

Weltweit sind derzeit um die 70 Mio. Glaukompatienten registriert. Nach der proliferativen diabetischen Retinopathie ist das Glaukom die zweitführende Ursache menschlicher Blindheit. Diese Gesamtsituation benötigt die Entwicklung neuer, viel effizienterer Konzepte. Innovative Strategien der prädiktiven, präventiven und personalisierten Medizin (PPPM) sollen einen wesentlichen Beitrag dazu leisten, die Glaukomvorsorge und eine personalisierte Behandlung der Betroffenen effektiv zu verbessern. Zu den komplexen PPPM-Maßnahmen gehören: Einführung individualisierter Patientenprofile, „Phänotypisierung“, molekulare Charakterisierung der Krankheitsvorstufen, innovative Screeningprogramme, Patientenstratifizierung, Früh- und Prädiktivdiagnose, gezielte Prävention und Ausarbeitung personalisierter Behandlungsmodalitäten. Die Hauptakteure sind die Glaukomforscher, Augenärzte, Hausärzte, Risikogruppen, spezialisierte medizinische Einheiten, betroffene Patienten und deren Familienmitglieder, Krankenkassen, politische Entscheidungsträger, diagnostische und pharmazeutische Industrie. Von einer effektiven Implementierung der PPPM-Maßnahmen werden sowohl die bereits aufgelisteten Gruppen als auch die Gesamtpopulation profitieren, da die ökonomisch gesehen wesentlich verbesserte Bilanz eine große Rolle im Gesundheitssektor spielen würde.

Abstract

Glaucoma is the second leading cause of blindness, with altogether about 70 million patients registered worldwide. These facts prompt us to reconsider currently applied concepts in overall glaucoma management. Innovative strategies of predictive, preventive and personalised medicine (PPPM) are expected to considerably improve disease prevention and personalised treatment. The comprehensive PPPM measures include the application of individualised patient profiles, “phenotyping”, molecular characterisation of the pre-lesions and disease stages, innovative screening programs, patient stratification, early and predictive diagnosis, targeted prevention, and the creation of personalised treatment algorithms. The main stakeholders are glaucoma-dedicated researchers, ophthalmologists, general practitioners, groups at risk, specialised medical units, affected patients and their family members, insurances, policy makers, and the diagnostic and pharmaceutical industries. Potential beneficiaries include these groups as well as society as a whole, due to financial savings in the healthcare expected.

Schlüsselwörter

prädiktive, präventive und personalisierte Medizin - Glaukom - Multiomics - Flammer-Syndrom - Innovation

Key words

predictive, preventive and personalised medicine - glaucoma - multiomics - Flammer syndrome - innovation

• Literatur

• 1 Golubnitschaja O, Baban B, Boniolo G. et al. Medicine in the early twenty-first century: paradigm and anticipation – EPMA position paper 2016. EPMA J 2016;
• 2 Golubnitschaja-Labudova O, Liu R, Decker C. et al. Altered gene expression in lymphocytes of patients with normal-tension glaucoma. Curr Eye Res 2000; 21: 867-876
• 3 de la Monte SM, Xu YY, Hutchins GM. et al. Developmental patterns of neuronal thread protein gene expression in Down syndrome. J Neurol Sci 1996; 135: 118-125
• 4 Tatton W, Chen D, Chalmers-Redman R. et al. Hypothesis for a common basis for neuroprotection in glaucoma and Alzheimerʼs disease: anti-apoptosis by alpha-2-adrenergic receptor activation. Surv Ophthalmol 2003; 48: S25-S37
• 5 Golubnitschaja O, Yeghiazaryan K, Flammer F. Glaucomatous optic Neuropathy: Risk Assessment and potential Targets for effective Prevention and Treatments tailored to the Patient. In: Mandel S. ed. Neurodegenerative Diseases: Integrative PPPM Approach as the Medicine of the Future. Vol. 3. Dordrecht, Heidelberg, New York, London: Springer; 2013
• 6 Hagan S, Martin E, Enríquez-de-Salamanca A. Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine. EPMA J 2016;
• 7 Mileguir D, Golubnitschaja O. Human saliva as a powerful source of information: multi-omics biomarker panels. EPMA J 2017;
• 8 Golubnitschaja O, Yeghiazaryan K, Liu R. et al. Increased expression of matrix metalloproteinases in mononuclear blood cells of normal-tension glaucoma patients. J Glaucoma 2004; 13: 66-72
• 9 Golubnitschaja O, Yeghiazaryan K, Wunderlich K. et al. Disease proteomics reveals altered basic gene expression regulation in leukocytes of normal-tension and primary open-angle glaucoma patients. Proteomics Clin Appl 2007; 1: 1316-1323
• 10 Golubnitschaja O, Flammer J. What are the biomarkers in glaucoma?. Surv Ophthalmol 2007; 52 (Suppl. 02) S155-S161
• 11 Yeghiazaryan K, Flammer J, Orgül S. et al. Vasospastic individuals demonstrate significant similarity to glaucoma patients as revealed by gene expression profiling in circulating leukocytes. Mol Vis 2009; 15: 2339-2348
• 12 Moenkemann H, Flammer J, Wunderlich K. et al. Increased DNA breaks and up-regulation of both G(1) and G(2) checkpoint genes p21(WAF1/CIP1) and 14-3-3 sigma in circulating leukocytes of glaucoma patients and vasospastic individuals. Amino Acids 2005; 28: 199-205
• 13 Golubnitschaja O, Yeghiazaryan K, Flammer J. Key molecular pathways affected by glaucoma pathology: is predictive diagnosis possible?. EPMA J 2010;
• 14 Yeghiazaryan K, Flammer J, Golubnitschaja O. Predictive molecular profiling in blood of healthy vasospastic individuals: clue to targeted prevention as personalised medicine to effective costs. EPMA J 2010;
• 15 Fraenkl SA, Golubnitschaja O, Yeghiazaryan K. et al. Differences in gene expression in lymphocytes of patients with high-tension, PEX, and normal-tension glaucoma and in healthy subjects. Eur J Ophthalmol 2013; 23: 841-849
• 16 Konieczka K, Ritch R, Traverso CE. et al. Flammer syndrome. EPMA J 2014;
• 17 Ahmed F, Brown KM, Stephan DA. et al. Microarray analysis of changes in mRNA levels in the rat retina after experimental elevation of intraocular pressure. Invest Ophthalmol Vis Sci 2004; 45: 1247-1258
• 18 Flammer J, Konieczka K. The discovery of the Flammer syndrome: a historical and personal perspective. EPMA J 2017;
• 19 Yeghiazaryan K, Flammer J, Wunderlich K. et al. An enhanced expression of ABC1 transporter in circulating leukocytes as a potential molecular marker for the diagnostics of glaucoma. Amino Acids 2005; 28: 207-211