The document discusses the chemistry of vision and color blindness. It begins with an introduction to retinal and its role in the eye as part of rhodopsin. When light is absorbed, retinal undergoes a conformational change to initiate a signal transduction pathway involved in vision. The document also discusses color vision and types of color blindness, as well as age-related macular degeneration which is linked to the buildup of a pigment called A2E.

1. The Chemistry of Vision April 17, 2008 Andrew Isleib Eric Sterne Jonathan Arnold Min Eun Lee Samara Shiromani

2. Agenda Introduction: Retinol and Eye Biology Chemistry of photoreception Color Vision and Color Blindness Macular Degeneration Concluding Remarks References

3. Introduction Conjugated systems - Dr. Phillips presented  -Carotene and retinol We will explain retinol’s role in vision and problems with vision Retinal - Aldehyde form of Retinol

4. Introduction: Sources of Vitamin A (Retinol) Humans cannot synthesize retinol from scratch Must ingest it directly or one of its precursors Animal sources of preformed vitamin A Liver, Milk, Butter, Cheese, Egg Yolk Provitamin A Carotenoids - convertible into vitamin A in body Beta-Carotene: Carrots, Spinich, Kale, Collard Greens, Sweet Potatoes, Pumpkin, Cantaloupe Lutein and Zeaxanthin

5. Introduction: The Eye Photoreception takes place in Rod and Cone cells of the retina Retina Rod Cells Cone Cell

6. - Opsin : Transmembrane G-Protein receptor Retinal: Chromaphore responsible for visible light absorption Retinal + Opsin = Rhodopsin Introduction: Rhodopsin

7. Introduction: Phototransduction A photon is absorbed by Rhodopsin which causes a conformational change in retinal 11-Cis Retinal

8. Introduction: Phototransduction The conformational change allows a G-protein to replace GDP with GTP - initiates transduction pathway. “ All-Trans” Retinal

9. Chemistry: Retinal Binding Mechanism of Schiff Base (Imine) formation Lysine side chain ends in -NH2

10. Chemistry: Rhodopsin Absorption  Positive charge distributed over conjugated  -bond system Stabilized by amino acid environment Narrows distance between HOMO and LUMO: Red Shift Entire photon must be absorbed Lower energy - Longer wavelength MO Energy HOMO LUMO HOMO LUMO Retinal Rhodopsin  max = 370nm  max = 498nm MO Energy

11. Color Vision: Cone Cells

12. Color Vision Trichromatic Vision: Red, Green Blue

13. Ishihara Test What numbers do you see?

14. Color Blindness Missing or defective pigment proteins for certain cone cell types ~8% of men, rare in women X chromosome codes for cones Types of Color Blindness Achromatopsia - black and white vision Dichromacy - 2 functioning cone types Anomalous Trichromacy - shifted cone absorption Non-Genetic Causes Disease, Accidents, Medication

15. Losing the Light Introduction to Age-Related Macular Degeneration

16. Normal Retina

17. Retina with AMD

18. Progression of AMD

19. Chemistry: A2E-epoxides A2E: autofluorescent pigment Pyridinium polar head group Two hydrophobic retinoid tails With light A2E creates epoxides at its C=C double bonds A2E-epoxides damage DNA DNA Lesions, Altered gene expression Potential link to AMD Vitamin E and C reduce A2E-epoxide

20. Conclusion Improved understanding of how we see? Just found out you are color blind? Support Group: http://dailystrength.org/c/Color-Blindness/support-group Age Related Macular Degeneration Antioxidants: protect your vision as you age See Better: keep up your supply of retinol Eat your carrots, greens, liver, etc.

21. References Shichi, Hitoshi. Biochemistry of Vision. New York: Academic Press, 1983. Chang, Raymond. Physical Chemistry for the Biosciences. Sausalito, California: United Science Books, 2005. Lugtenburg, Johan, Muradin-Szweykowska, Maria, Heeremans, Carola, and Pardoen, Johannes A. “Mechanism for the opsin shift of retinal's absorption in bacteriorhodopsin.” J. Am. Chem. Soc., 108, 11, 3104 - 3105, 1986, 10.1021/ja00271a050. Wachtler, T. Doi, E., Lee, T.-W., & Sejnowski, T.J. (2007). &quot;Cone selectivity derived from the responses of the retinal cone mosaic to natural scenes. Journal of Vision, 7(8):6, 1-14. <http://www.journalofvision.org/7/8/6/>, doi:10.1167/7.8.6. Casidy, Rachel and Regina Frey. “’I Have Seen the Light!’: Vision and Light-Induced Molecular Changes.” Department of Chemistry. 2000. Washington University. 25 Mar 2008, <http://www.chemistry.wustl.edu/~edudev/LabTutorials/Vision/Vision.html>. Ishihara Test for Color Blindness. <http://www.toledo-bend.com/colorblind.Ishihara.html>

22. References Ophartd, Charles, E. “Chemistry of Vision.” 2003. Elmhurst College. 15 Mar 2008. <http://www.elmhurst.edu/~chm/vchembook/531vision.html>. Ophartd, Charles, E. “Beta-Carotene and Vitamin A.” 2003. Elmhurst College. 15 Mar 2008. <http://www.elmhurst.edu/~chm/vchembook/532vitaminA.html> Dutton, Frank. “Ishihara Test for Color Blindness.” 2 Apr 2008. <http://www.toledo-bend.com/colorblind/Ishihara.html> Sparrow, Janet R., Heidi R. Vollmer-Snarr, Jilin Zhou, Young P. Jang, Steffen Jockusch, Yasuhiro Itagaki, and Koji Nakanishi. “A2E-epoxides Damage DNA in Retinal Pigment Epithelial Cells: Vitamin E and Other Antioxidants Inhibit A2E-Epoxide Formation.” The Journal of Biological Chemistry. Vol. 278, No. 20, Issue of May 16, pp. 18207–18213, 2003. Wade, L. G. Jr. Organic Chemistry. Sixth Edition, New Jersey: Pearson Prentice Hall, 2006 Yamadaa, A. T. Kakitania, S. Yamamotob and T. Yamato. “A computational study on the stability of the protonated Schiff base of retinal in rhodopsin.” Chemical Physical Letters, Vol. 366, Issues 5-6, 20 December, pp. 670-675, 2002

23. References Nolan, Donia, E. “Normal Age Related Vision Loss and Related Services for the Elderly.” 2002. Stephen F. Austin State University. 20 Mar. 2008. <http://hubel.sfasu.edu/research/donia/aging_visual_changes.htm> Bowmaker J.K. and Dartnall H.J.A., &quot;Visual pigments of rods and cones in a human retina.&quot; J. Physiol. 298: pp501-511 (1980). “ Sensory Systems.” 2006. Bellarmine University Department of Biology. 2 Apr. 2008. <http://cas.bellarmine.edu/tietjen/HumanBioogy/sensory_systems.htm> Gill, Cynthia. “Web Page for Bio 416L.” 2007. Hampshire College. 2 Apr. 2008 <http://helios.hampshire.edu/~cjgNS/sputtbug/416l/HumanPhys.html> Polans A, Baehr W, and Palczewski K. “Turned on by Ca2+! The physiology and pathology of Ca2+-binding proteins in the retina.” Trends in Neurosciences. vol. 19(12). 1996. Pages 547-554 Ramón y Cajal, Santiago. “Drawing of Layers of Retina.” Online Image. 1911. Wikipedia. 21 Mar. 2008. <http://en.wikipedia.org/wiki/Image:Fig_retine.png> Escher, M.C. “Eye.” Online Image. 1946. Pictures by M.C Escher. 15 Mar 2008. <http://aaronbaird.net/pictures/Escher/> Omikron, “Magnified image of the rods and cones of the human eye.” Free Health Encyclopedia. 3 Apr. 2008. <http://www.faqs.org/health/Sick-V1/Color-Blindness.html>

24. Introduction Conjugated systems - Dr. Phillips presented  -Carotene and retinal We will explain retinal’s role in vision and problems with vision

25. ß-Carotene

26. Vitamin A - All Trans Retinol Humans cannot synthesize retinol from scratch Must ingest it directly or one of its precursors

27. Retinal to Vitamin A

28. Ishihara Test