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Dr. Tsang: Stem Cell Treatment Research and Its Possible Applicability to Achromatopsia
- 1. Edward S. Harkness Eye Institute Stephen Tsang, MD, PhD [email_address] Greater NY Center
- 3. No Gap 20/200, 24 yo 20/80, 15 yo
- 5. Optically Empty Gap 20/150, 48 yo 20/160, 23 yo
- 10. The human induced pluripotent stem (iPS) cells have been produced by reprogramming somatic cells (skin fibroblast) with a set of 4 transcription factors. The human iPS-cells show striking similarities in their morphological, gene expression, and functional characteristics to human ES-cells, and seem to have acquired the critical ES-cell characteristics of unlimited growth and potential to differentiate to all cell types of human body. Fibroblasts and iPS Cells. (A) Fibroblasts taken from patient skin. (B) Fibroblasts after treatment with OCT4, SOX2, KLF4, and cMYC. (C) iPS colonies after SB431542 and PD0325901 selection. (D) Detail of iPS colonies pictured in (C). Induced Pluripotent Stem Cells can be derived from a patient skin fibroblasts
- 11. Study Design Skin Biopsy Stem Cell Colonies Stem Cells Differentiation toward Retinal Cells Transplantation
- 12. Human Induced Pluripotent Stem (iPS) Cells Skin Fibroblasts Stem Cells Stem Cell Colonies Retinal Cells Yao Li, M.D.
- 13. Differentiation of Stem Cells into Photoreceptors Control Stem Cells [email_address]
- 14. ES cells can Differentiate into Photoreceptors Negative Control Pdeg -IRES-EGFP R1#49 Pol2-EGFP (Positive Control) [email_address]
- 15. Optically Empty Gap 20/150, 48 yo 20/160, 23 yo
- 17. Pablo Picasso. Breakfast of a blind man . 1903.
- 19. -/- Five Years old
- 20. -/- Five Years old
- 21. -/- Sixteen Years old
- 22. -/- Sixteen Years old
- 23. Fundus photo of Rpe65 rd12 /Rpe65 rd12 Pang et al. 2005 [email_address] 3 M 5 M 7 M 15 M
- 24. Severely attenuated ERG of Rpe65 rd12 /Rpe65 rd12 1 M 8 M
- 25. Histology of Rpe65 rd12 /Rpe65 rd12 Pang et al. 2005 6 W 3 M 7 M 15 M
- 27. Mouse Fetal Transplantation 10 days Post-transplantation 1 M Post-transplantation
- 28. ERG change after transplantation
- 29. N=1 N=1 N=1 N=2 N=2 N=10 N=10 N=13 N=13 Width of Outer Nuclei (rows of nuclei)
- 30. C2J-YFP Embryonic Stem (ES) cells [email_address]
- 31. Study Design PA6 cells (feeder cells) Embryonic stem cells Subretinal injection into postnatal 5 days old mice In vitro differentiation
- 32. [email_address]
- 34. 9.3--> 28 week
- 36. Transplant Survival Nan-Kai Wang, M.D.
- 37. ES Transplant Survival Control Transplant Transplant Nan-Kai Wang, M.D.
- 38. [email_address]
- 39. ERG Analysis
- 40. ERG Analysis 40 0 20 1 2 3 4 5 6 7 Months Post-transplantation Maximal Responses b-wave Enhancement (μV) ** * * p<0.05 ** p<0.01
- 41. Injection Technique 40 0 20 ES-RPE PBS Mit-C PA6 Mit-C ESC Injection Components (3 Months Post-Injection) Maximal Responses b-wave Enhancement (μV) ** * p<0.05 ** p<0.01
- 51. Tao et al, 2002 IOVS In mice with retinal degeneration
- 53. Copyright ©2006 by the National Academy of Sciences Sieving, Paul A. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 3896-3901 Fig. 1. Visual acuity (VA) changes of the study eyes and fellow control eyes of the 10 participants over the 6-month implant period. Grouped by lower-dose implants (Phase IA) and higher-dose implants (Phase IB)
- 54. Copyright ©2006 by the National Academy of Sciences Sieving, Paul A. et al. (2006) Proc. Natl. Acad. Sci. USA 103, 3896-3901 Fig. 2. Histology in longitudinal section of a CNTF device after removal at 6 months from the study eye of a Phase-IB participant
- 56. Second Sight: Retinal Prosthesis Trial Completes First Phase Of Testing Ft. Lauderdale, Fla., May 8 – Researchers from the Keck School of Medicine of the University of Southern California, its Doheny Retina Institute and Second Sight, LLC, are reporting on the initial results of their groundbreaking, FDA-approved feasibility trial of an intraocular retinal prosthesis that appears to be able to restore some degree of sight to the blind.
- 59. 100
- 60. 101
Editor's Notes
- IR imaging reveals speckled hyper- and hypo-reflectivity. On FAF, there is a hypoautofluorescent center surrounded by a hyperautofluorescent ring. SD-OCT imaging shows a clear optical gap with absent IS/OS, as well as an elevated ELM that is hyper-reflective. There is also choroidal hyper-reflectivity,indicating RPE atrophy.
- Some with loss of IS, some both. Not clearly correlated with visual acuity
- IR imaging reveals a hypo-reflective outer ring, and a hyper-reflective central lesion. On FAF, there is a slightly hyperautofluorescent outer ring with a more hypoautofluorescent center. The IS/OS loss on OCT corresponds to the inner margin of the outer hypoautofluorescent ring on FAF as well as the hyporeflective area on IR.
- Some with loss of IS, some both. Not clearly correlated with visual acuity
- Pablo Picasso. Breakfast of a blind man . 1903. This man has deeply sunken eye suggesting that he probably suffers from phthisical bulbi as a result of ocular trauma or failed ocular surgery. The alternative explanation is Leber's congenital amaurosis in which prolonged eye rubbing leads to orbital fat atrophy and enophthalmos. Oil on canvas. The Metropolitan Museum of Art, New York, USA.
- 6, 12, 21
- 6, 12, 21