Chemistry Of Vision Final

The Chemistry of VisionApril 17, 2008

Andrew Isleib

Eric Sterne

Jonathan Arnold

Min Eun Lee

Samara Shiromani

Agenda

• Introduction: Retinol and Eye Biology

• Chemistry of photoreception

• Color Vision and Color Blindness

• Macular Degeneration

• Concluding Remarks

• References

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

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

Introduction: The Eye

Photoreception takes place in Rod and Cone cells of the retina

Retina

Rod Cells

Cone Cell

- Opsin : Transmembrane G-Protein receptor

- Retinal: Chromaphore responsible for visible light absorption

- Retinal + Opsin = Rhodopsin

Introduction: Rhodopsin

Introduction: Phototransduction

A photon is absorbed by Rhodopsin which causes a conformational change in retinal

11-Cis Retinal

Introduction: Phototransduction

The conformational change allows a G-protein to replace GDP with GTP - initiates transduction pathway.

“All-Trans” Retinal

Chemistry: Retinal Binding

• Mechanism of Schiff Base (Imine) formation– Lysine side chain ends in -NH2

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

En

erg

y

HOMO

LUMO

HOMO

LUMO

Retinal Rhodopsinmax=370nm

max=498nm

MO

En

erg

y

Color Vision: Cone Cells

Color Vision

• Trichromatic Vision: Red, Green Blue

Ishihara TestWhat numbers do you see?

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

Losing the LightIntroduction to Age-Related Macular Degeneration

Normal Retina

Retina with AMD

Progression of AMD

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

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.

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). "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>

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

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., "Visual pigments of rods and cones in a human retina." 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>