1. GENE THERAPY FOR RED- GREEN COLOR BLINDNESS Mary Ellen Sweeney, Biomedical Engineering, University of Rhode Island Sophomore, BME 281 First Presentation

2. OVERVIEW: RED-GREEN COLOR BLINDNESS  A.K.A.- “Daltonism” named after chemist/physicist, John Dalton, (who had colorblindness).  Responsible for his Atomic Theory & the first recognized account of red-green colorblindness.  Most common single locus genetic disorder.  Inherited in an X-linked recessive manner.  Affects 6% of men worldwide.  Men are more likely to be color blind as opposed to females.  Because the genes responsible for the inherited genetic disorder are on the X chromosomes.  Can present itself at any age. Daltonism. (2013, August 28). Retrieved November 29, 2015.

3. ENCHROMA  Alternative approach to red-green color blindness correction.  Company whom under an NIH SBIR grant dedicated the past decade+ to developing a line of corrective & innovative eyewear products.  Noninvasive, temporary “external” fix to color blindness through lens technology.  The EnChroma team has developed a line of glasses which suit any & all of a customers needs. EnChroma | Color For the Color Blind. (2015). Retrieved November 28, 2015.

4. THE HISTORY OF GENE THERAPY  Existed since the 1960’s/70’s.  Still in its infancy.  Defined as “the transplantation/injection of normal genes into cells to replace missing or defective ones.”  An experimental technique used to treat or prevent genetic disorders. What is gene therapy? (2015, November 23). Retrieved November 29, 2015, http://ghr.nlm.nih.gov/handbook/therapy/genetherapy

5. GENE THERAPY IN TERMS OF COLOR BLINDNESS  An invasive approach for the means of achieving a permanent cure.  Requires an injection/implementation of a normal transgene into the retina of the eye.  Series of potential risks.  Retinal injection may cause irritation or infection to the retina.  Could result in vision loss or retinal detachment.  Negative psychological effects may also be associated with suddenly being able to see new colors. Neitz, J. & Neitz, M. (2011). The genetics of normal and defective color vision. Vis Res, 51, 633-651.

6. CASE STUDY  Test subjects: Squirrel Monkeys  Behaviorally tested  Possessed the ability to distinguish between blue & yellow while red & green were indistinguishable from gray.  Through focus on the S (short), M (middle), & L (long) cones in the retina & the manipulation of the transgene, color blindness was cured in the monkey. Neitz, J. & Neitz, M. (2011). The genetics of normal and defective color vision. Vis Res, 51, 633-651.

7.  “This 2-stage model has become the accepted dogma for color vision.”  These monkeys are dichromat’s & possess only M & S cones (protanope).  The addition of the 3 rd class of cone, the M cones, leads to new activity patterns exiting the retina.  Their M vs. M receptive fields leaving the retina carried only light-dark edge information, & could travel down one of two pathways, one with S-cone centers or one with M cone centers & S-cone inputs to the surround.  Wavelengths of the activity patterns are altered. Mancuso, K., Mauck, M., Kuchenbecker, J., Neitz, M., & Neitz, J. (2010). A multi-stage color model revisited: Implications for a gene therapy cure for red-green colorblindness. Retrieved November 28, 2015, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044922/figure/F1/.

8. CONCLUSIONS DRAWN THROUGH EXPERIMENTATION  Through R&D & concentration on the field of color vision/color vision gene therapy we know the 4 main hue perceptions are blue, yellow, red & green.  Contributions from S, M, & L cone types are wavelength-sensitive.  Through the addition of the missing photo pigment, the M cone, into the midget ganglion cell receptive fields, the blue-yellow circuits split further resulting in the correction of red-green color blindness.  Confirmed by putting monkeys through a series of behavioral tests. Mancuso, K., Mauck, M., Kuchenbecker, J., Neitz, M., & Neitz, J. (2010). A multi-stage color model revisited: Implications for a gene therapy cure for red-green colorblindness. Retrieved November 28, 2015.

9. GeneTherapy. (n.d.). Retrieved November 28, 2015, http://www.neitzvision.com/content/genetherapy.html.

10. RISKS VS. BENEFITS This variation of gene therapy has yet to be tested on humans, therefore the actual risks are currently unknown. Potential risks though include,  Gene therapy may not work in humans as well as it did in relation to monkeys.  The side effects are unknown due to a lack of experimentation.  Potential side effects could include…  Irritation, infection, permanent retinal detachment, or even blindness.  Psychological effects resulting from suddenly being able to see new colors. GeneTherapy. (n.d.). Retrieved November 28, 2015, http://www.neitzvision.com/content/genetherapy.html.

11. RISKS VS. BENEFITS CONTINUED…  Obviously a series of benefits could be the result of human experimentation.  If experimentation is a success, it would be a permanent cure to red- green color blindness.  Would be beneficial to the scientific community, allowing scientists to understand the potential of gene therapy in enhancing/restoring individuals visual capacity. GeneTherapy. (n.d.). Retrieved November 28, 2015, http://www.neitzvision.com/content/genetherapy.html.

12. ETHICS  Ethical issues are the roadblock to conducting research in human beings…  In order for human experimentation to take place they must receive approval from…  The NIH (National Institute of Health).  ORDA (Office of Recombinant DNA Activities)/ RAC (Recombinant DNA Advisory Committee).  FDA (Food and Drug Administration).  In addition to approval of an IND (Investigational New Drug Application) from the FDA.  Approval from an IRB (Institutional Review Board) where the experimental process/study will take place. GeneTherapy. (n.d.). Retrieved November 28, 2015, http://www.neitzvision.com/content/genetherapy.html.

13. OVERALL,  No one knows how gene therapy could affect humans in comparison to monkeys.  Finding willing & informed test subjects may pose as a difficulty.  But,  If the FDA does approve human testing the scientific community would be able to understand the potential of gene therapy in restoring an individual to their full visual capacity.  The permanent cure in squirrel monkeys has set the precedent.  EnChroma provides a temporary “external” fix to color blindness through lens technology, but gene therapy could provide the permanent cure to the estimated 300 million worldwide that to date possess this color vision deficiency.

14. WORKS CITED  Daltonism. (2013, August 28). Retrieved November 29, 2015, http://www.medicinenet.com/script/main/art.asp?articlekey=7036  EnChroma | Color For the Color Blind. (2015). Retrieved November 28, 2015, http://enchroma.com/.  GeneTherapy. (n.d.). Retrieved November 28, 2015, http://www.neitzvision.com/content/genetherapy.html.  Mancuso, K., Mauck, M., Kuchenbecker, J., Neitz, M., & Neitz, J. (2010). A multi- stage color model revisited: Implications for a gene therapy cure for red-green colorblindness. Retrieved November 28, 2015, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3044922/figure/F1/.  Neitz, J. & Neitz, M. (2011). The genetics of normal and defective color vision. Vis Res, 51, 633-651.  What is gene therapy? (2015, November 23). Retrieved November 29, 2015, http://ghr.nlm.nih.gov/handbook/therapy/genetherapy

15. QUESTIONS?