Group of Age-Related Macular Degeneration

 

Group Leader

Kai Kaarniranta
Professor

Faculty of Health Sciences
School of Medicine
University of Eastern Finland
Yliopistonranta 1C, 70210 Kuopio
Finland

Tel.: +358-44 059 32 90
E-mail: kai.kaarniranta (at) uef.fi

 

Post-doctoral Researchers

Szabolcs Felszeghy
Juha Hyttinen
Niko Kivinen
Mika Reininsalo

Doctoral Students

Mooud Amirkavei 
Francesco Dragoni
Iswariyaraja Sridevi Gurubaran
Eveliina Korhonen (main supervisor Anu Kauppinen, Immuno-Ophthalmology)
Ali Koskela
Mikko Liukkonen
Tuomas Paimela
Jussi Paterno
Niina Piippo (main supervisor Anu Kauppinen, Immuno-Ophthalmology)
Johanna Ruuth
Toni Tamminen
Maija Toppila (main supervisor Anu Kauppinen, Immuno-Ophthalmology)
Johanna Viiri

Research Nurses

Helvi Käsnänen
Tanja Jurvanen

Technician

Anne Seppänen

Major Research Interests

AMD  research group aims at studying regulatory mechanism of protein aggregation, lysosomal and autophagy clearance in retinal pigment epithelial cells. We aim at find novel autophagy (http://nordicautophagy.org/home.php)  linked therapy for age-related macular degeneration (AMD).

AMD is the leading cause of blindness and is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the central retina responsible for fine and color vision. The protein aggregation is strongly associated with senescence of retinal pigment epithelial cells and development of AMD. Intracellular lysosomal lipofuscin and extracellular drusen protein deposits are strongly associated with AMD. To date there is strong evidence that in AMD proteasomal and lysosomal clearance is disturbed, resulting in increase protein aggregation and AMD development.
Some of protein aggregates are subsequently secreted out of cells that might be initiative stimuli for drusen formation and advancing of severe AMD. Our laboratory aims at understanding the function of molecular chaperones in proteasomal and lysosomal clearance in RPE cells.

Selected Publications

Loss of NRF-2 and PGC-1α genes leads to retinal pigment epithelium damage resembling dry age-related macular degeneration. Felszeghy S, Viiri J, Paterno JJ, Hyttinen JMT, Koskela A, Chen M, Leinonen H, Tanila H, Kivinen N, Koistinen A, Toropainen E, Amadio M, Smedowski A, Reinisalo M, Winiarczyk M, Mackiewicz J, Mutikainen M, Ruotsalainen AK, Kettunen M, Jokivarsi K, Sinha D, Kinnunen K, Petrovski G, Blasiak J, Bjørkøy G, Koskelainen A, Skottman H, Urtti A, Salminen A, Kannan R, Ferrington DA, Xu H, Levonen AL, Tavi P, Kauppinen A, Kaarniranta K. Redox Biol. 2018 Sep 14;20:1-12. doi: 10.1016/j.redox.2018.09.011. [Epub ahead of print]

Oxidative Stress is the Principal Contributor to Inflammasome Activation in Retinal Pigment Epithelium Cells with Defunct Proteasomes and Autophagy. Piippo N, Korhonen E, Hytti M, Kinnunen K, Kaarniranta K, Kauppinen A. Cell Physiol Biochem. 2018;49(1):359-367. doi: 10.1159/000492886. Epub 2018 Aug 23.

Mechanistical retinal drug targets and challenges. Kaarniranta K, Xu H, Kauppinen A. Adv Drug Deliv Rev. 2018 Feb 15;126:177-184. doi: 10.1016/j.addr.2018.04.016. Epub 2018 Apr 23.

Autophagy Stimulus Promotes Early HuR Protein Activation and p62/SQSTM1 Protein Synthesis in ARPE-19 Cells by Triggering Erk1/2, p38MAPK, and JNK Kinase Pathways. Marchesi N, Thongon N, Pascale A, Provenzani A, Koskela A, Korhonen E, Smedowski A, Govoni S, Kauppinen A, Kaarniranta K, Amadio M. Oxid Med Cell Longev. 2018 Feb 8;2018:4956080. doi: 10.1155/2018/4956080. eCollection 2018.

Outcome of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration in real-life setting. Kataja M, Hujanen P, Huhtala H, Kaarniranta K, Tuulonen A, Uusitalo-Jarvinen H. Br J Ophthalmol. 2018 Jul;102(7):959-965. doi: 10.1136/bjophthalmol-2017-311055. Epub 2017 Oct 26.

Depletion of the Third Complement Component Ameliorates Age-Dependent Oxidative Stress and Positively Modulates Autophagic Activity in Aged Retinas in a Mouse Model. Rogińska D, Kawa MP, Pius-Sadowska E, Lejkowska R, Łuczkowska K, Wiszniewska B, Kaarniranta K, Paterno JJ, Schmidt CA, Machaliński B, Machalińska A. Oxid Med Cell Longev. 2017;2017:5306790.

The Finnish national guideline for diagnosis, treatment and follow-up of patients with wet age-related macular degeneration.Tuuminen R, Uusitalo-Järvinen H, Aaltonen V, Hautala N, Kaipiainen S, Laitamäki N, Ollila M, Rantanen J, Välimäki S, Sipilä R, Laukkala T, Komulainen J, Tommila P, Immonen I, Tuulonen A, Kaarniranta K. Acta Ophthalmol. 2017 Jul;95(A105 Suppl):1-9. doi: 10.1111/aos.13501.

Autophagy Regulates Proteasome Inhibitor-Induced Pigmentation in Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells. Juuti-Uusitalo K, Koskela A, Kivinen N, Viiri J, Hyttinen JMT, Reinisalo M, Koistinen A, Uusitalo H, Sinha D, Skottman H, Kaarniranta K. Int J Mol Sci. 2017 May 19;18(5).

Clearance of autophagy-associated dying retinal pigment epithelial cells - a possible source for inflammation in age-related macular degeneration. Szatmári-Tóth M, Kristóf E, Veréb Z, Akhtar S, Facskó A, Fésüs L, Kauppinen A, Kaarniranta K, Petrovski G. Cell Death Dis. 2016 Sep 8;7(9):e2367.

Defects in retinal pigment epithelial cell proteolysis and the pathology associated with age-related macular degeneration. Ferrington DA, Sinha D, Kaarniranta K .Prog Retin Eye Res. 2016 Mar;51:69-89. doi: 10.1016/j.preteyeres.2015.09.002.