Retinal progenitor sheet transplantation and demonstration of vision improvement in models of retinal degeneration and ultimately in retinal degeneration patients (Retinitis Pigmentosa, age-related macular degeneration)
Dr. Seiler’s Ph.D. in 1985 (LMU University of Munich, Max Planck Institute for Psychiatry, Dept. Neurochemistry) focused on neurotrophic factors in the central nervous system, followed by postdoctoral studies in retinal transplantation in Winston-Salem, NC and Boston, MA. She was Assistant Professor at the University of Louisville, KY from 1993-2002, and at the Doheny Eye Institute, USC Department of Ophthalmology 2002-2006.
In a collaboration lasting more than 30 years with her colleague, Dr. Robert Aramant, they developed and refined a unique procedure of retinal progenitor sheet transplantation, which has demonstrated improvement of visual responses in the superior colliculus in 4 different retinal degeneration models (RCS rats, rd mice, rho S334ter line 3 and line 5 rat models of fast and slow retinal degeneration). Dr. Seiler participated in Phase I and II clinical trials to transplant sheets of fetal retina with its RPE to patients with retinal degeneration (retinitis pigmentosa and age-related macular degeneration). The phase II trial showed improvements of visual acuity (EDTRS) in 7 of 10 patients (reference https://escholarship.org/uc/item/4783d911).
From 2007-2014, she was the lead researcher of the retina project of the Research group of Dr. Hans Keirstead at UC Irvine (now CEO at AIVITA Biomedical Inc.). In 2014, she received a 3-year Early Translational grant from CIRM with the goal of developing human embryonic stem cells to transplantable 3-D sheets of retinal progenitor cells for vision restoration. In 2018, she received a 4.7 million TRAN1 grant (2.5 years) entitled “Morphological and functional integration of stem cell derived retina organoid sheets into degenerating retina models.” that will develop this application towards a treatment for Retinitis Pigmentosa (see press release http://www.som.uci.edu/news_releases/Seiler_CIRM_grant2_06222018.asp).
In 2021, she received a 5-year R01 grant from the National Eye Institute, entitled "Integration and functionality of retinal organoid transplants". This grant is in collaboration with Dr. Biju Thomas, USC. This study will determine (1) whether transplants of hESC-derived retina together with a supporting layer of RPE promote better visual improvement than transplant of hESC-retina alone by using an RD rat model with dysfunctional RPE that does not reject human cells. (2) In addition, we will investigate the mechanism of visual improvement with hESC-retinal transplants by creating RD rats with labels that identify specific host cells and investigating host-transplant connectivity.
Postdoctorate, Retinal Transplantation, Wake Forest University, Winston-Salem, NC 1986-1987
Postdoctorate, Retinal Transplantation, Eye Research Institute, Boston, MA 1987-1988
Scientific Associate, Retinal Transplantation, Eye Research Institute, Boston, MA, 1989-1992
Assistant Professor, Ophthalmology & Visual Sciences; Anatomy & Neurobiology, University of Louisville School of Medicine, 1993-2002
Assistant Professor, Doheny Eye Institute; Ophthalmology; Cell & Neurobiology, Keck School of Medicine (USC), 2002-2006
Project Scientist, Anatomy & Neurobiology, UC Irvine School of Medicine, 2007 – 2014
Project Scientist, Physical Medicine & Rehabilitation, UC Irvine School of Medicine, 2014-2015
Assistant Professor, Physical Medicine & Rehabilitation, UC Irvine School of Medicine, 2015 -
The goal of Dr. Seiler’s research is to develop retinal progenitor sheet transplants as a clinical treatment for retinal diseases such a Retinitis Pigmentosa and age-related macular degeneration, which affect both photoreceptors and retinal pigment epithelium (RPE). The current focus of her research is to develop human embryonic stem cells (hESCs) into transplantable sheets of 3D retina (organoids) and RPE and to demonstrate vision restoration at the level of the superior colliculus and visual cortex in rat models of retinal degeneration. In the frame of her CIRM TRAN1 grant, pre-clinical experiments have demonstrated further the benefits of retinal organoid transplantation, resulting in a pre-IND submitted to the FDA. A new 5-year NIH grant will study co-grafting hESC-retina with RPE and create a new rat model with specifically labeled cell types to study transplant-host connectivity.
1988 Travel fellowship to attend the NATO Advanced Workshop "The Neurobiology of the Inner Retina", Oldenburg, Germany
1989 Bursary (Travel fellowship) for IIIrd International Symposium on Neural Transplantation, Cambridge, U.K.
1992 Travel fellowship to attend the ICER Meeting in Stresa, Italy
Xue Y, Browne AB, Tang WC, Delgado J, McLelland BT, Nistor G, Keirstead HS, Chen JT, Chew K, Lee N, Seiler MJ*. Retinal Organoids Long-term Functional Characterization Using Two-Photon Fluorescence Lifetime and Hyperspectral Microscopy; Frontiers in Cellular Neuroscience - Cellular Neurophysiology: 15:796903 (2021, in press); special research topic “Innovative Cell and Tissue Culture Approaches for Modeling Mammalian Retinal Development, Pathologies, Regeneration, and Therapies in a Dish” (accepted 11-26-21). doi: 10.3389/fncel.2021.796903. * - corresponding author
Thomas BB, Lin B, Martinez-Camarillo JC, Zhu D, McLelland BT, Nistor G, Keirstead HS, Humayun MS, Seiler MJ*. Co-grafts of human embryonic stem cell derived retina organoids and retinal pigment epithelium in immunodeficient retinal degenerate Royal College of Surgeons rats. Frontiers in Neuroscience, 15:752958 (2021); special issue “Stem Cell-Based Therapy in Retinal Degeneration”; doi:10.3389/fnins.2021.752958. PMID: 34764853; PMCID: PMC8576198. * - corresponding author
McAleer S, Fast A, Xue Y, Seiler MJ, Tang WC, Balu M, Baldi P, Browne AW. Deep learning-assisted multiphoton microscopy to reduce light exposure and expedite imaging in tissues with high and low light sensitivity. TVST, 10(12):30 (2021). PMID: 34668935; DOI: 10.1167/tvst.10.12.30
Xue Y, Seiler MJ, Tang WC, Wang JY, Delgado J, McLelland BT, Nistor G, Keirstead HS, Browne AW. Retinal organoids on-a-chip: a micro-millifluidic bioreactor for long-term organoid maintenance. Lab Chip, 21:3361 (2021). DOI:10.1039/d1lc00011j. PMID 34236056
Nair RDS, Seiler MJ, Patel KH, Thomas V, Martinez JC, Humayun MS, Thomas BB. Tissue engineering strategies for retina regeneration. Applied Sciences 2021, 11, 2154. https://doi.org/10.3390/app11052154 (accepted 3/23/21; published online 2/28/21) Invited review (peer-reviewed).
Singh RK, Binette F, Seiler MJ, Petersen-Jones SM, Nasonkin IO. Pluripotent stem cell-based organoid technologies for developing next-generation vision restoration therapies of blindness. J Ocul Pharmacol Ther 37(3):147-156 (2021); doi: jop.2020.0016. PMID 33052761; PMC8060716. Invited review (peer-reviewed).
Lin B, McLelland BT, Nistor G, Aramant RB, Thomas BB, Keirstead HS, Seiler MJ*. Retina organoid transplants develop photoreceptors and improve visual function in RCS rats with RPE dysfunction. Invest Ophthalmol Vis Sci, 61(11):34 (2020). PMID: 32945842; PMCID: PMC7509771; DOI: 10.1167/iovs.61.11.34 * - corresponding author
Singh RK, Winkler P, Binette F, Glickman RD, Seiler M, Petersen-Jones SM, Nasonkin IO. Development of a protocol for maintaining viability while shipping organoid-derived retinal tissue. J Tissue Eng Regen Med.;14:388–394 (2020). DOI: 10.1002/term.2997; selected for journal cover. PMID: 31908157
Foik AT, Lean GA, Scholl LR, McLelland BT, Mathur A, Aramant RB, Seiler MJ, Lyon DC. Detailed visual cortical responses generated by retinal sheet transplants in rats with severe retinal degeneration. J. Neurosci, 38(50):10709-10724 (2018) (selected for press release at SFN 2018) doi: 10.1523/JNEUROSCI.1279-18.2018. PMID: 30396913; PMC: 6290293;
Thomas BB, Zhu D, Lin T-C, Kim YC, Seiler MJ, Martinez-Camarillo JC, Lin B, Shad Y, Hinton DR. A New Immunodeficient Retinal Dystrophic Rat Model for Transplantation Studies Using Human Derived Cells. Graefe’s Arch Clin Exp Ophthalmol, 256 (11):2113–2125 (2018); https://doi.org/10.1007/s00417-018-4134-2. PMID30215097
Lin B, McLelland BT, Mathur A, Aramant RB, Seiler MJ*. Sheets of human retinal progenitor transplants improve vision in rats with severe retinal degeneration. Experimental Eye Research, 174:13-28 (2018). https://doi.org/10.1016/j.exer.2018.05.017. PMID29782826. * - corresponding author
McLelland BT, Lin B, Mathur A, Aramant RB, Thomas BB, Nistor G, Keirstead HS, Seiler MJ*. Transplanted hESC-retina organoid sheets differentiate, integrate and improve visual function in retinal degenerate rats. Invest Ophthalmol Vis Sci 59:2586-2603 (2018). doi:10.1167/iovs.17-23646. PMC5968836. * - corresponding author
Seiler MJ. hESC-derived photoreceptors survive and integrate better in immunodeficient retina. Invited Editorial. Stem Cell Investigation 4:70 (2017); doi: 10.21037/sci.2017.08.05. PMID 28920063; PMC5590018
Lin T-C, Seiler MJ, Zhu D, Falabella P, Hinton DR, Clegg DO, Humayun MS, Thomas BB. Assessment of safety and functional effect of stem cell-based therapeutic approaches using retinal degenerative animal models. Stem Cells International, 2017:9428176 (2017); https://doi.org/10.1155/2017/9428176. PMID 28928775; PMC5592015. Invited review (peer-reviewed).
Seiler MJ*, Lin R, McLelland BT, Mathur A, Lin B, Sigman J, De Guzman A, Kitzes LM, Aramant RB, Thomas BB. Vision Recovery and Connectivity by Fetal Retinal Sheet Transplantation in an Immunodeficient Retinal Degenerate Rat Model. Invest. Ophthalmol Vis Sci, 58:614-630 (2017). DOI 10.1167/iovs.15-19028. PMID 28129425. * - corresponding author
Seiler MJ, Aramant RB, Jones MK, Ferguson D, Bryda E, Keirstead HS. A new immunodeficient pigmented retinal degenerate rat strain to study transplantation of human cells without immunosuppression. Graefe’s Arch Clin Exp Ophthalmol, 252:1079-1092 (2014). DOI 10.1007/s00417-014-2638-y.
Seiler MJ, Aramant RB. Cell replacement and visual restoration by retinal sheet transplants. Prog Retin Eye Res, 31:661-687 (2012). Invited review (peer-reviewed)
Seiler MJ*, Jones BW*, Aramant RB, Yang PB, Keirstead HS, Marc RE. Computational molecular phenotyping of retinal sheet transplants to rats with retinal degeneration. Eur J. Neurosci, 35:1692–1704 (2012) (Figure 9A selected for cover of EJN's Virtual Issue: Disorders of the Nervous System)
* - equal contribution
Martinez-Navarrete G, Seiler MJ, Aramant RB, Fernandez-Sanchez L, Pinilla I, Cuenca N. Retinal Degeneration in Two Lines of Transgenic S334ter Rats. Exp Eye Res 92: 227-237 (2011)
Yang PB*, Seiler MJ*, Aramant RB, Yan F, Mahoney MJ, Kitzes LM, Keirstead HS. Trophic Factors GDNF and BDNF Improve Function of Retinal Sheet Transplants. Exp Eye Res 91: 727-738 (2010)
Nistor G*, Seiler MJ*, Yan F, Ferguson D, Keirstead HS. Three-Dimensional Early Retinal Progenitor 3D Tissue Constructs Derived from Human Embryonic Stem Cells. J. Neurosci. Methods, 190:63–70 (2010)
* - equal contribution
Seiler MJ*, Rao B*, Aramant RB, Yu L, Wang Q, Kitayama E, Pham S, Yan F, Chen Z, Keirstead HS. Three-dimensional Optical Coherence Tomography Imaging of Retinal Sheet Implants in Live Rats. J. Neurosci. Methods, 188: 250–257 (2010)
* - equal contribution
Seiler MJ, Aramant RB, Thomas BB, Peng Q, Sadda SR, Keirstead HS. Visual restoration and transplant connectivity in degenerate rats implanted with retinal progenitor sheets. Eur J. Neurosci, 31(3):508-520 (2010)
Seiler MJ, Aramant RB, Seeliger M, Bragadottir R, Mahoney M, Narfstrom K. Functional and structural assessment of retinal sheet allograft transplantation in feline hereditary retinal degeneration. Veterinary Ophthalmology, 12(3):158–169 (2009)
Seiler MJ, Thomas BB, Chen Z, Wu R, Sadda SR, Aramant RB. Retinal transplants restore visual responses - Transsynaptic tracing from visually responsive site in the superior colliculus (SC) labels transplant neurons. Eur J. Neurosci, 28:208-220 (2008) (selected for journal cover)
Radtke ND, Aramant RB, Petry HM, Green PT, Pidwell DJ, Seiler MJ. Vision Improvement in Retinal Degeneration Patients by Implantation of Retina Together with Retinal Pigment Epithelium. Am J Ophthalmol, 146:172-182 (2008)
R01 EY031834-01A1: M. Seiler (PI) - 05/01/2021 – 03/30/2026 -
National Institutes of Health (NIH)/National Eye Institute (NEI);
"Integration and functionality of retinal organoid transplants"
TRAN1-10995: M. Seiler (PI). - 09/01/2018-02/28/2021 (NCE to 12/31/21)
CIRM (California Inst. f. Regenerative Medicine) Partnering Opportunity for Translational Research Projects. "Morphological and functional integration of stem cell derived retina organoid sheets into degenerating retina models".
Sue & Bill Gross Stem Cell Research Center (SCRC)