Credentials

B.Sc. - Molecular Biology and Biochemistry with Industrial Placement, University of Durham, Durham, UK

Ph.D. - Medicine, Subspeciality: Neuroscience, University of Leiden, Leiden, NL

Research Focus: Cornea and Ocular Surface Disease, Glaucoma

Summary of Research Interests

Our laboratory is interested in drug discovery and drug delivery for ophthalmic disorders. In particular, we investigate intracellular signaling pathways that contribute to the generation of cellular oxidative and nitric stress in a variety of cell types, including neurons, glia, and epithelial cells. Employing a broad pharmacological approach that utilizes cell and molecular biology, biochemistry, microscopy and electrophysiology, we aim to identify new drug targets and delivery strategies for two disease indications: neurodegeneration (glaucoma) and ocular surface disease (dry eye disease). As part of our glaucoma program, we are investigating the biomechanical forces and neuron-glia interactions in the optic nerve head to advance gene therapy approaches for this debilitating disease. Our dry-eye disease program focuses on the development of novel topical nanoparticle formulations that exert potent anti-inflammatory and anti-oxidant properties.

Publications

2022

• Ghosh AK, Bacellar-Galdino M, Iqbal S, Pappenhagen NE, Kaja S. Topical Porphyrin Antioxidant Protects Against Ocular Surface Pathology in a Novel Rabbit Model for Particulate Matter-Induced Dry Eye Disease. J Ocul Pharmacol Ther. 2022 May;38(4):294-304. doi: 10.1089/jop.2021.0131. Epub 2022 Apr 4. PMID: 35384749; PMCID: PMC9125571.
• Lelyte I, Ahmed Z, Kaja S, Kalesnykas G. Structure-Function Relationships in the Rodent Streptozotocin-Induced Model for Diabetic Retinopathy: A Systematic Review. J Ocul Pharmacol Ther. 2022 May;38(4):271-286. doi: 10.1089/jop.2021.0128. Epub 2022 Mar 22. PMID: 35325558; PMCID: PMC9125572.
• Losenkova K, Takeda A, Ragauskas S, Cerrada-Gimenez M, Vähätupa M, Kaja S, Paul ML, Schmies CC, Rolshoven G, Müller CE, Sandholm J, Jalkanen S, Kalesnykas G, Yegutkin GG. CD73 controls ocular adenosine levels and protects retina from light-induced phototoxicity. Cell Mol Life Sci. 2022 Feb 25;79(3):152. doi: 10.1007/s00018-022-04187-4. PMID: 35212809; PMCID: PMC8881442.

2021

• Acevedo-Jake A, Shi S, Siddiqui Z, Sanyal S, Schur R, Kaja S, Yuan A, Kumar VA. Preclinical Efficacy of Pro- and Anti-Angiogenic Peptide Hydrogels to Treat Age-Related Macular Degeneration. Bioengineering(Basel). 2021 November; 8(12): 190. DOI: 10.3390/bioengineering8120190. PMID: 34940343. PMCID: PMC8698576.
• Ghosh AK, Thapa R, Hariani HN, Volyanyuk M, Ogle SD, Orloff KA, Ankireddy S, Lai K, Žiniauskaitė A, Stubbs EB Jr., Kalesnykas G, Hakkarainen JJ, Langert KA, Kaja S. Poly(lactic-co-glycolic acid) Nanoparticles Encapsulating the Prenylated Flavonoid, Xanthohumol, Protect Corneal Epithelial Cells from Dry Eye Disease-Associated Oxidative Stress. Pharmaceutics. 2021 August; 13(9):1362. doi.org/10.3390/pharmaceutics13091362. PMID: 34575438. PMCID: PMC8471707.

2020

• Ghosh AK, Rao VR, Wisniewski VJ, Zigrossi AD, Floss J, Koulen P, Stubbs Jr. EB, Kaja S. Differential Activation of Glioprotection Intracellular Signaling Pathways in Primary Optic Nerve Head Astrocytes after Treatment with Different Classes of Antioxidants. Antioxidants (Basel). 2020 April; 9(4): 324. doi: 10.3390/antiox9040324. PMCID: PMC7222350.

2019

• Ziniauskaite A, Ragauskas S, Ghosh AK, Thapa R, Roessler AE, Koulen P, Kalesnykas G, Hakkarainen JJ, Kaja S. Manganese (III) Tetrakis (1-Methyl-4Pyridyl) Porphyrin, a Superoxide Dismutase Mimetic, Reduces Disease Severity in In Vitro and In Vivo Models for Dry-Eye Disease. The Ocular Surface. 2019 April; 17(2): 257-264. doi: 10.1016/j.jtos.2019.02.006. PMCID: PMC6570415.
• Kouzoukas DE, Schreiber JA, Tajuddin NF, Kaja S, Neafsey EJ, Kim HY, Collins MA. PARP inhibition in vivo blocks alcohol-induced brain neurodegeneration and neuroinflammatory cytosolic phospholipase A2 elevations. Neurochemistry International. 2019 October; 129: 104497. doi: 10.1016/j.neuint.2019.104497. PMCID: PMC6760246.
• Breuer EK, Fukushiro-Lopes D, Dalheim A, Burnette M, Zartman J, Kaja S, Wells C, Campo L, Curtis KJ, Romero-Moreno R, Littlepage LE, Niebur GL, Hoskins K, Nishimura MI, Gentile S. Potassium channel activity controls breast cancer metastasis by affecting β-catenin signaling. Cell Death and Disease. 2019 February; 10(3):180. doi: 10.1038/s41419-019-1429-0. PMCID: PMC6385342.

2018

• Ragauskas S, Kielczewski E, Vance J, Kaja S, Kalesnykas G. In Vivo Multimodal Imaging and Analysis of Mouse Laser-Induced Choroidal Neovascularization Model. Journal of Visualized Experiments. 2018 January; 131: 56173. doi: 10.3791/56173. PMCID: PMC5908670.
• Rosen SM, Kaja S, De Alba F. Transient Colorblindness Associated with Sildenafil and Tadalafil. JAMA Ophthalmology. 219 January; 137(1): 117-118. doi: 10.1001/jamaophthalmol.2018.4716. PMID: 30286227.

2017

• Huang J, Romero-Suarez S, Lara N, Mo C, Kaja S, Brotto L, Dallas SL, Johnson ML, Jähn K, Bonewald LF, Brotto M. Crosstalk between MLO-Y4 osteocytes and C2C12 muscle cells is mediated by the Wnt/β-catenin pathway. JBMR Plus. 2017 October; 1(2): 86-100. doi: 10.1002/jbm4.10015. PMCID: PMC5667655.
• Sandoval A, Duran P, Gandini MA, Andrade A, Almanza A, Kaja S, Felix R. Regulation of L-type CaV1.3 channel activity and insulin secretion by the cGMP-PKG signaling pathway. Cell Calcium. 2017 September; 66: 1-9. doi: 10.1016/j.ceca.2017.05.008. PMCID: PMC5776030.
• Maciulaitiene R, Pakuliene G, Kaja S, Pauza DH, Kalesnykas G, Januleviciene I. Glioprotection of Retinal Astrocytes After Intravitreal Administration of Memantine in the Mouse Optic Nerve Crush Model. Medical Science Monitor. 2017 March; 23: 1173-79. doi: 10.12659/msm.899699. PMCID: PMC5352005.
• Kaja S, Payne AJ, Naumchuk N, Koulen P. Quantification of Lactate Dehydrogenase for Cell Viability Testing Using Cell Lines and Primary Cultured Astrocytes. Current Protocols in Toxicology. 2017 May; 72(1): 2.26.1- 2.26.10. doi: 10.1002/cptx.21. PMCID: PMC5501254.

2016

• Hakkarainen JJ, Reinasalo M, Ragauskas S, Seppanen A, Kaja S, Kalesnykas G. Acute cytotoxic effects of marketed ophthalmic formulations on human corneal epithelial cells. International Journal of Pharmaceutics. 2016 September; 511(1):73-78. doi: 10.1016/j.ijpharm.2016.06. PMID: 27374205.
• Means JC, Gerdes BC, Kaja S, Sumien N, Payne AJ, Stark DA, Borden PK, Price JL, Koulen P. Caspase-3-Dependent Proteolytic Cleavage of Tau Causes Neurofibrillary Tangles and Results in Cognitive Impairment During Normal Aging. Neurochem Res. 2016 May; 41: 2278-2288. doi: 10.1007/s11064-016-1942-9. PMCID: PMC4965284.
• Richter F, Koulen P, Kaja S. N-Palmitoylethanolamine Prevents the Run-down of Amplitudes in Cortical Spreading Depression Possibly Implicating Proinflammatory Cytokine Release. Scientific Reports. 2016 March; 6: 23481. doi: 10.1038/srep23481. PMCID: PMC4804239.

2015

• Kaja S, Payne AJ, Naumchuk Y, Levy D, Zaidi DH, Altman AM, Nawazish S, Ghuman JK, Gerdes BC, Moore MA, Koulen P. Plate reader-based cell viability assays for glioprotection using primary rat optic nerve head astrocytes. Experimental Eye Research. 2015 September; 138: 159-166. doi: 10.1016/j.exer.2015.05.023. PMCID: PMC4553084.
• Kaja S, Payne AJ, Patel KR, Naumchuk Y, Koulen P. Differential subcellular Ca2+ signaling in a highly specialized subpopulation of astrocytes. Experimental Neurology. 2015 March; 265: 59-68. doi: 10.1016/j.expneurol.2014.12.014. PMCID: PMC4346429.
• Kaja S, Shah AA, Haji SA, Patel KB, Naumchuk Y, Zabaneh A, Gerdes BC, Kunjukunju N, Sabates NR, Cassell MA, Lord RK, Pikey KP, Poulose A, Koulen P. Nampt/PBEF/visfatin serum levels – a new biomarker for retinal blood vessel occlusions. Clinical Ophthalmology. 2015 April, 9: 611-18. doi: 10.2147/OPTH.S80784. PMCID: PMC4396426.

2014

• Breuer EK, Fukushiro-Lopes D, Dalheim A, Burnette M, Zartman J, Kaja S, Wells C, Campo L, Curtis KJ, Romero-Moreno R, Littlepage LE, Niebur GL, Hoskins K, Nishimura MI, Gentile S. Potassium channel activity controls breast cancer metastasis by affecting β-catenin signaling. Cell Death and Disease. 2019 February; 10(3):180. doi: 10.1038/s41419-019-1429-0. PMCID: PMC6385342.