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Center for the Prevention and Treatment of Visual Loss

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Dr. Kuehn

 

Markus Keuhn, Ph.D. 
 

 

Markus Kuehn, Ph.D.

Investigator, Center for the Prevention and Treatment of Visual Loss
Professor, Department of Ophthalmology & Visual Sciences, University of Iowa

Phone: (319) 335-9565

E-mail: markus-kuehn@uiowa.edu

Education

MS, Botany, Goethe University (Frankfurt)

PhD, Cell and Molecular Biology, St. Louis University

Post Doctoral, Ophthalmology, The University of Iowa


Research Interests

1) Neuroimmunology in progressive neurodegenerative diseases. Damage to the central nervous system, including the eye, can result in both acute and chronic inflammation responses. Acute inflammation is often desirable and aids in the removal of cell debris or damaged cells. On the other hand, chronic inflammation is frequently associated with slow but progressive damage and may continue even after the primary damage has been resolved. Findings from Dr. Kuehn's lab have demonstrated that in animal models glaucoma can be accompanied by an adaptive immune response directed against retinal cells. The laboratory has also developed methods to transplant immune cells from the blood of patients into mice and have demonstrated that cells from some patients also cause glaucoma – like damage in the mice. We are currently carrying out a study to determine if this response is predictive of glaucomatous damage in donating patients. If this is the case immunomodulating therapy may be of benefit to some glaucoma patients.



2) Regeneration of the Trabecular Meshwork. Some pressure within the eye is required to retain proper shape and function, but elevated intraocular pressure significantly contributes to the development of glaucoma. The trabecular meshwork is a small tissue within the eye with the function of maintaining healthy intraocular pressure. With age and particular with glaucoma cells are lost from this tissue and its ability to carry out its function becomes compromised. Dr. Kuehn's laboratory has pioneered methods to replace these lost cells with induced pluripotent stem cells. These cells can be derived from patients and can then be differentiated into the trabecular meshwork cells. Transplanting these cells into the eyes of animal models of glaucoma leads to restoration of normal intraocular pressure. Current studies are directed to investigate a similar approach can also be useful for of glaucoma patients.

 Transplanted stem cell derived trabecular meshwork cells (green) integrated into the tissue of a human donor eye.

Publication Highlights

Neuroimmunology:

  1. Gramlich OW, Ding QJ, Zhu W, Cook A, Anderson MG, Kuehn MH. Adoptive transfer of immune cells from glaucomatous mice provokes retinal ganglion cell loss in recipients. Acta Neuropathol Commun. 2015 Sep 15;3:56. doi: 10.1186/s40478-015-0234-y. PMID: 26374513; PMCID: PMC4591529.
  2. Gramlich OW, Godwin CR, Heuss ND, Gregerson DS, Kuehn MH. T and B Lymphocyte Deficiency in Rag1-/- Mice Reduces Retinal Ganglion Cell Loss in Experimental Glaucoma. Invest Ophthalmol Vis Sci. 2020 Dec 1;61(14):18. doi: 10.1167/iovs.61.14.18. PMID: 33320171; PMCID: PMC7745626.
  3. Gramlich OW, Godwin CR, Wadkins D, Elwood BW, Kuehn MH. Early Functional Impairment in Experimental Glaucoma Is Accompanied by Disruption of the GABAergic System and Inceptive Neuroinflammation. Int J Mol Sci. 2021 Jul 15;22(14):7581. doi: 10.3390/ijms22147581. PMID: 34299211; PMCID: PMC8306430.

 

Regeneration:

  1. Ding QJ, Zhu W, Cook AC, Anfinson KR, Tucker BA, Kuehn MH. Induction of trabecular meshwork cells from induced pluripotent stem cells. Invest Ophthalmol Vis Sci. 2014 Oct 8;55(11):7065-72. doi: 10.1167/iovs.14-14800. PMID: 25298418; PMCID: PMC4224582.
  2. Zhu W, Gramlich OW, Laboissonniere L, Jain A, Sheffield VC, Trimarchi JM, Tucker BA, Kuehn MH. Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo. Proc Natl Acad Sci U S A. 2016 Jun 21;113(25):E3492-500. doi: 10.1073/pnas.1604153113. Epub 2016 Jun 6. PMID: 27274060; PMCID: PMC4922164.
  3. Zhu W, Zhang X, Wu S, Wang N, Kuehn MH. iPSCs-Based Therapy for Trabecular Meshwork. Handb Exp Pharmacol. 2023;281:277-300. doi: 10.1007/164_2023_671. PMID: 37495850.