Rhodopsin

1. Rhodopsin By: Shannon Cikowski and Molly Smith

2. What is Rhodopsin? • Visual pigment and protein 9 • “Visual purple” 1 • Chromo protein 9 • Located in rod cells of the retina1

3. Function of Rhodopsin • It functions in dim light 9 • It bleaches when it is exposed to bright light 9 • The RHO gene makes rhodopsin 10 • Rhodopsin is necessary for vision in low light 10 • Rhodopsin is attached to 11-cis-retainal 10

4. Rhodopsin Cycle - Breaking down • Rhodopsin has two components, scotopsin and 11-cis-retainal 13 • When they combine they make a rhodopsin molecule 13 • Light converts 11-cis-retainal into 11-trans –retinal 13 Rhodopsin breaks off from scotopsin and into component parts 13

5. Rhodopsin Cycle - Building up • Takes place by two slide pathways 13 • 11-trans-retainal is converted into 11-cis-retainal 13 • The scotopsin combines with 11-cis-retainal to make rhodopsin13

6. Mutations in the Rhodopsin Gene • Can cause: • Retinitis pigmentosa11 • Can be inherited three ways: Autosomal recessive, Autosomal dominant, and X-linked recessive 8 • Rhodopsin mutations cause many cases of autosomal dominant retinitis pigmentosa 1 • Autosomal dominant – receiving one abnormal gene from one parent and that is how the disease is inherited 5 • A mutation in the rhodopsin gene is one of the several causes of this disease 1 • Congenital Standing Night Blindness 1 • Four different mutations in the RHO gene cause this 10

7. Retinitis Pigmentosa • Retinitis Pigmentosa (RP) • Rhodopsin mutations cause autosomal dominant retinitis pigmentosa 1 • Affects over 1.5 million people worldwide 1 • Type of retinal degeneration 3 • Rod cells typically affected first 3 • RP causes the breakdown of photoreceptor cells, which capture and process light 8 • More common in males 3 • Symptoms: 1 • Night blindness • Progressive decrease in vision • Slow adjustments to light and dark areas 8 • Tunnel vision / Loss of peripheral vision 8 • Majority experience first symptoms between 10 and 30 1 • Blindness

9. Retinitis Pigmentosa - Mutations • Studies set out to find the different mutations in rhodopsin that cause this disease • Bensen et al studied 150 patients with autosomal dominant retinitis pigmentosa 2 • Found 17 mutations in the study that caused the disease – variety 2

10. Retinitis Pigmentosa - Mutations • Single-base substitutions 2 • Most common rhodopsin mutation found was in codon 23: 2 mRNA sequence to Amino Acid • Mutation: CAC -> Histidine • Normal: CCC -> Proline • Incorrect amino acid sequence results in malfunctioning protein • Another common mutation in codon 347 2 • CTG instead of CCG • Codes for leucine instead of proline

11. Retinitis Pigmentosa - Treatment • No known cure for retinitis pigmentosa 8 • Treatments and genetic testing are available 3 • Vitamin A treatments and the Argus Retinal Prosthesis are semi-successful methods 6, 8 • Idea is to insert healthy genes into the retina to fix the problem 8 • Many clinical trials are trying to use gene therapy to treat retinitis pigmentosa caused by rhodopsin mutations 3 • Trials with treating rodent models have been occurring 1

12. Retinitis Pigmentosa – Stem Cell Treatment • Researchers are trying to use stem cells to become new photoreceptors for people who have diseases such as RP 7 • Some scientists are working on using stem cells derived from the patient’s skin or blood 7 • In this stem cell treatment, proteins are used to alter the stem cells so they know to turn into retinal cells 7 • Rhodopsin gene is involved7

13. Retinitis Pigmentosa (RP) • Genable is launching clinical trials using gene therapies for RP caused by rhodospin mutations in 2014 4 • ReNeuron is also opening trials using stem cells to help RP in 2013 7 • Foundation Fighting Blindness, among other organizations, are funding research as well 3

14. Congenital Standing Night Blindness • Lose rod function 12 - affects vision in dim conditions • Cone function is unchanged 12 • The mutations are found around the retinal attachment in rod cells12

15. Night Blindness Causes15 Treatments15 • Eye drops • Vitamin A supplementation • Clinical trials for gene therapy as a future treatment • RHO gene mutation • Lack of vitamin A • Refsum’s disease • Retinitis pigmentosa • Unable to see clearly at night and in dim light • Headache • Dry eyes • Blurred vision Symptoms15

16. Night Blindness Stem Cell Treatment • Scientists are also working with embryonic stem cells and induced pluripotent stem cells to treat night blindness and lost vision 14 • Columbia University Medical Center made advances using stem cell treatment14 * • No stem cell treatment is available currently, but many clinical trials are working towards this treatment now 14

17. Works Cited 1. Narins, B. (2006). Rhodospin. Retrieved from http://go.galegroup.com/ps/i.do?id=GALE%7CCX3451500373&v=2.1&u=lans19446&it=r&p=GVRL&sw=w. 2. Berson, E., McGee, T., Cowley, G., Hahn, L., Dryja, T. (1991). Mutation Spectrum of the Rhodopsin Gene among Patients with Autosomal Dominant Retinitis Pigmentosa. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC52716/pdf/pnas01070-0516.pdf. 3. Foundation Fighting Blindness (N.D.). What is Retinitis Pigmentosa?. Retrieved from http://www.blindness.org/index.php?option=com_content&id=50&Itemid=67#treatments. 4. Foundation Fighting Blindness (2012, Sept 7). Simpler Gene Therapy Envisioned for Some Forms of Dominant RP. Retrieved from http://www.blindness.org/index.php?view=article&id=3267%3Asimpler-gene-therapy-envisioned-for-some-forms-of-dominant-rp&option=com_content&Itemid=119. 5. Medicine Plus (2013, March 22). Autosomal Dominant. Retrieved from http://www.nlm.nih.gov/medlineplus/ency/article/002049.htm. 6. National Horizon Scanning Center (2011, June). Argus II™ Retinal Prosthesis System for Peripheral Retinal Degeneration. Retrieved from http://readtiger.com/wkp/en/Argus_Retinal_Prosthesis. 7. Shaberman, B. (2013 Jan 23). Safely Harnessing the Power of Stem Cells. Retrieved from http://www.blindness.org/blog/index.php/safely-harnessing-the-power-of-stem-cells/#more-2056 . 8. National Human Genome Research Institute (2012, Oct. 23). Learning About Retinitis Pigmentosa. Retrieved from http://www.genome.gov/13514348.

18. Works Cited 9. Encyclopedia Britannia. (2013). Rhodopsin. Encyclopedia Britannia. Retrieved from: http://www.britannica.com/EBchecked/topic/501725/rhodopsin. 10. Department of health and human services. (2013). RHO. Genetics Home Reference. Retrieved from: http://ghr.nlm.nih.gov/gene/RHO. 11. US national library of medicine. (2012). Retinitis Pigmentosa. Pubmed heath. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002024/. 12. University of Alabama. (unknown). Abstract. Pubmed.gov. Retrieved from: http://www.ncbi.nlm.nih.gov/pubmed/20238025. 13. Anatomy AND Physiology of the eye. (Unknown). Rhodopsin Cycle. Rhodopsin Cycle. Retrieved from: http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/rhodopsn.htm. 14. Blue Sky Science.(2012). Restoring vision in night blindness. Speaking of research. Retrieved from: http://speakingofresearch.com/2012/04/27/restoring-vision-in-night-blindness- mice-point-way-to-stem-cell-therapy/. 15. Ultimate Cosmetics. (2003). Ultimate Cosmetics. Night Blindness. Retrieved from: http://eye.ultimate-cosmetics.com/night-blindness.html.