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Selected Publications

that have given systematic and encouraging results
on the road to where we have arrived successfully today.

All papers were published in “refereed” and respected journals
which means
that experts have examined and criticized the

papers before approval for publication.

  • 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. Reference

    This study crossed NIH immunodeficient rats that have no T-cells with transgenic rats with a mutant rhodopsin (S334ter-3). The resulting rat strain can be used to test the effect of human tissue/cell on retinal degeneration without having to use immunosuppression.
  • 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). Reference

    This study used a state-of-the-art analysis method, of cell types in transplant and host, computational molecular phenotyping. The data indicated that horizontal cells and amacrine cells are involved in a novel circuit between transplant and host, generating alternative signal pathways between transplant and degenerating host retina.
  • 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. Reference

    This study compared the effects of the trophic factors BDNF and GDNF on the functional outcome of fetal retinal sheet transplants, and demonstrated that visual restoration is better with laminated transplants. Transplantation of non-retinal neural progenitor tissue (cortex) had no effect.
  • 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.  Reference

    This study showed in vivo imaging of retinal sheet transplants in live rats by serial scans of Fourier-Domain 3D ocular coherence tomography (OCT). The laminar structure of transplants, placement of the transplants in relation to the optic disk and surgical defects could be correctly detected by OCT with an accuracy of 83-98%. Histology of transplants was correlated with OCT results.
  • 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. Reference

    This was the first indisputable demonstration by confocal and electron microscopy of synapse formation between transplant and host; and a correlation with the visual improvement.
  • Seiler MJ, Thomas BB, Chen Z, Wu R, Sadda SR, Aramant RB. Retinal transplants restore visual responses: trans-synaptic tracing from visually responsive sites labels transplant neurons. Eur J. Neurosci, 28:208-220, 2008. Reference

    This experiment proved that the connectivity of the transplant with the host was responsible for the visual improvement.
  • 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. Reference

    This paper presents the positive results of the Phase II clinical study spanning from one to over six years in ten patients: four macular degeneration and six retinitis pigmentosa patients.
  • Seiler MJ, Thomas BB, Chen Z, Arai S, Chadalavada S, Mahoney M, Sadda SR, Aramant RB. BDNF-Treated Retinal Progenitor Sheets Transplanted to Degenerate Rats - Improved Restoration of Visual Function. Exp Eye Res. 86(1): 92-104, 2008. Reference

    Before transplantation, the transplant was coated with a growth factor (BDNF). This factor was released slowly in the host and increased the visual function of the transplanted rats with over 20%.
  • Thomas BB, Arai S, Ikai Y, Qiu G, Chen Z, Aramant RB, Sadda SR, Seiler MJ.Retinal Transplants Evaluated By Optical Coherence Tomography in Photoreceptor Degenerate Rats. J Neurosci Methods, 151: 186-193, 2006. Reference

    This study used optical coherence tomography (OCT) for screening of retinal transplants in the live rat eye. In 62% of transplanted rats, OCT revealed the presence of a subretinal graft. OCT imaging data correlated mostly with transplant morphology.
  • Seiler MJ, Sagdullaev BT, Woch G, Thomas BB, Aramant RB.  Transsynaptic virus tracing from host brain to subretinal transplants. Eur J Neurosci, 21:161-172, 2005. Reference

    A tracer was injected into the visual center in the brain, migrated through the optic nerve to the host retina, and labeled cells in the transplant indicating that the transplant had synaptic connections with the brain.
  • Thomas BB, Seiler MJ, Sadda SR, Coffey PJ, Aramant RB. Optokinetic test to evaluate visual acuity of each eye independently. J Neurosci Meth, 138:7-13,  2004. Reference

    This experiment is called optokinetic test and showed that eyesight was saved in transplanted rats with retinal degeneration.
  • Radtke ND, Aramant RB, Seiler MJ, Petry HM, Pidwell D. Vision change after sheet transplant of fetal retina with retinal pigment epithelium to a patient with Retinitis Pigmentosa. Arch Ophthalmol, 122: 1159-1165, 2004. Reference

    This clinical paper describes visual improvement in one retinitis pigmentosa patient.
  • Thomas BB, Seiler MJ, Sadda SR, Aramant RB. Superior colliculus responses to light preserved by transplantation in a slow degeneration rat model. Exp Eye Res, 79(1): 29-39, 2004. Reference

    These two papers used newly created experimental rats that have been genetically manipulated. A human “sick” gene has been introduced in the photoreceptors so that the rats develop blindness like in human retinitis pigmentosa patients.

    It was demonstrated that eyesight has been saved and restored in both rat models. It was also proven that no rescue of host photoreceptors took place so the improvement was caused by the transplants.  The two rat strains differ in that one strain develops blindness much faster than the other.
  • Sagdullaev BT, Aramant RB, Seiler MJ, Woch G, McCall MA. Retinal transplantation-induced recovery of retinotectal visual function in a rodent model of retinitis pigmentosa. Invest Ophthalmol Vis Sci, 44(4):1686-1695, 2003. Reference
  • Aramant RB, Seiler MJ. Transplanted sheets of human retina and retinal pigment epithelium develop normally in nude rats. Exp Eye Res, 75(2):115-125, 2002. Reference

    This was a very important preclinical experiment. Could human retinal pigment epithelium be transplanted together with neuronal retina (containing photoreceptors), and survive long term? – The answer was yes. 

    This could be achieved in albino nude rats with no functional immune system that would not reject the foreign human transplant. The RPE could stay as a monolayer after 10 months and show a normal interaction with the transplanted photoreceptors. This set the important stage to introduce this approach (to transplant both sheets together) to human clinical trials.
  • Radtke ND, Seiler MJ, Aramant RB, Petry HM, Pidwell DJ. Transplantation of intact sheets of fetal neural retina with its RPE in retinitis pigmentosa patients. Am J Ophthalmol, 133(4):544-550, 2002. Reference

    This paper was the Phase I clinical trial which demonstrated the safety of transplanting sheets of fetal retina together with its RPE to patients with Retinitis Pigmentosa.
  • Woch G, Aramant RB, Seiler MJ, Sagdullaev BT, McCall MA. Retinal transplants restore visual responses in rats with photoreceptor degeneration. Invest Ophthalmol Vis Sci, 42 (7): 1669-76, 2001. Reference

    This is the first paper that showed restoration of vision in a blind rat by transplanting both retinal pigment epithelium and photoreceptors. Transplanted rat eyes were illuminated and the electrical responses were recorded in the visual center of the brain. Only responses from the transplanted eye could be recorded.

    To start testing the function of the transplants’ effect on the host, it was a challenge to develop the testing model of choice and the setup of instruments to measure light responses in the superior colliculus (SC) in the brain.  The outcome was the demonstration that the light sensitivity could be restored in the RCS rat co-transplanted with RPE and neuronal retina.  We demonstrated that there was no rescue of host photoreceptors.
  • Seiler MJ, Liu OL, Cooper NGF, Callahan TL, Petry HM, Aramant RB. Selective photoreceptor damage in albino rats using continuous blue light – a protocol useful for retinal degeneration and transplantation research. Graefe’s Arch Clin Exp Ophthalmol, 238:599-607, 2000. Reference

    We managed to create a needed new experimental animal model with a damaged retina to test the transplants. 

    In albino rats, 2-3 days of continuous moderate blue light selectively destroyed most of the photoreceptors and spared the RPE. There was a time window of 3-4 weeks after light damage to perform the transplantation before the RPE degenerated. An interesting aspect of our results was that the transplant saved the RPE from degeneration and the RPE apparently had a normal interaction with transplant photoreceptors and host choroid even after 9‑10 months (as shown in the 1998 paper).
  • Seiler MJ, Aramant RB, Ball SL. Photoreceptor function of retinal transplants implicated by light-dark shift of S-antigen and rod transducin. Vision Res., 39:2589-2596, 1999. Reference

    This paper showed that the transplanted photoreceptors can transform light into electrical signals, the ultimate function of normal photoreceptors

    There are some models of retinal degeneration in which the histology of photoreceptors can look perfectly normal, but the shift of phototransduction proteins cannot be seen. This is a sign that the photoreceptors are not functional. The shift of phototransduction proteins is a very sensitive test that clearly shows that our transplant photoreceptors can function like normal photoreceptors
    .
  • Aramant RB, Seiler MJ, Ball SL. Successful cotransplantation of intact sheets of fetal retina with retinal pigment epithelium. Invest Ophthalmol Vis Sci, 40:1557-1564, 1999. Reference

    We know that most patients with retinal diseases need both new retinal pigment epithelium (RPE) and photoreceptors. Therefore, we developed the surgery procedure to transplant a fresh sheet of RPE together with photoreceptors.  The RCS rat was the most suitable model. It was one of the most difficult technical and encouraging achievements so far in our research.
  • Seiler MJ, Aramant RB. Intact sheets of fetal retina transplanted to restore damaged rat retinas. Invest. Ophthalmol. Vis. Sci., 39:2121-2131, 1998. Reference

    This paper shows enormously encouraging results – that the transplants can repair an area of a damaged retina and develop cell types in layers that appear to be functional like normal retinal cells.
    Observe the good integration that can be seen between transplant and host. Sometimes, it can be impossible to define the interface even in electron microscope.
  • Aramant RB, Seiler MJ.  Organized embryonic retinal transplants to normal or light-damaged rats.  Soc. Neurosci. Abstr. 21:1308, 1995

    This was the first demonstration that a retinal sheet transplant could develop to resemble a normal retina.
  • Aramant R, Seiler M.  Fiber and synaptic connections between embryonic retinal transplants and host retina.  Experimental Neurology, 133:1-12, 1995. Reference

    The contact points between nerve cells are called synapses.  Synapses are a prerequisite for nerve cells to talk with each other, e.g. between transplant cells and host cells.

    This paper established that transplant processes can make all types of synapses with the host retina.
    Transplant was in a host injury site inside of retina.  This study gave hope that transplants placed in the subretinal space (in the true target area) might also have the potential to establish synaptic connections with the host retina.

Reviews

  • Seiler MJ, Aramant RB. Cell replacement and visual restoration by retinal sheet transplants. Progress in Retinal and Eye Res, 31:661-687, 2012. Reference

    This important paper is our most recent extensive overview of 25 years of research, covering most of the field of retinal transplantation.
  • Seiler MJ, Aramant RB, Keirstead HS. Retinal Transplants: Hope to Preserve and Restore Vision Optics and Photonics News, 19(4): 37-42, 2008. Reference
  • Aramant RB, Radtke N.D., Seiler MJ. Recent results in retinal transplantation give hope for restoring vision. In Retinal Degenerations: Genetics, Progression, and Therapeutics, eds. J. Tombran-Tink and C. Barnstable, Humana Press, Totowa, NJ, 2006, pp.363-381
  • Seiler MJ, Aramant RB. Transplantation of neuroblastic progenitor cells as a sheet preserves and restores retinal function. Seminars in Ophthalmology, 20:31-42, 2005 Reference
  • Aramant RB, Seiler MJ. Progress in retinal sheet transplantation. Progress in Retinal and Eye Research 23(5): 475-494, 2004. Reference
  • Aramant RB, Seiler MJ. Retinal transplantation – advantages of intact fetal sheets. Progress in Retinal and Eye Research 21:57-73, 2002. Reference