Sight Restoring Polymers

1. Sight Restoring Polymers http://www.inovanz.com/cornea-healing/ Anna BurgessLuke Smith Zack Mobley XuanGao

2. Abstract: • Poly(3-hexylthiophene) • A polymer created from organic electronics and biological substrates. • This layer of polymer placed on a damaged retina mixed with nerve cells produces an active retina. • The recreated retina responds to the feeling of light. • Extended research in organic polymers to restore blindness in humans. • Could lead to advanced prosthetic implants. http://cdn.physorg.com/newman/gfx/news/hires/2013/researchersr.jpg

3. Abstract Organic Conducting Polymers http://upload.wikimedia.org/wikipedia/commons/thumb/a/a0/ConductivePoly.png/400px-ConductivePoly.png

4. Introduction • What is a degenerate retina? • What are organic conducting polymers? • What makes this particular case special? • What means were used to quantify the data? • What are the real world applications? • What other advantages come from further research of the such polymers? Degenerated Retina http://www.lookfordiagnosis.com/mesh_info.php?term=Retinal+Degeneration&lang=1

5. Degenerate Retina http://cdn.physorg.com/newman/gfx/news/hires/2013/researchersr.jpg

6. What are organic conducting polymers? • Organic Conducting Polymers • Found with the mixing of organic electronics and biological substrates • Used for creating cellular scaffolds, neural probes, biosensors and actuators for drug release https://www.google.com/search?q=cellular+scaffolding&source=lnms&tbm=isch&sa=X&ei=0dVpUcj4JMeF2AX0joHAAg&ved=0CAoQ_AUoAQ&biw=1280&bih=620#imgrc=Vlgb8npqQoB0QM%3A%3BcpkbsRTe96qLXM%3Bhttp%253A%252F%252Fwww.ozbiosciences.com%252Fimages%252Fstories%252FOZB%252FProducts%252FthreeD%252Fblanc-ombres-trans-scaffold.gif%3Bhttp%253A%252F%252Fwww.ozbiosciences.com%252F3d-fect-2.html%3B1282%3B784

7. Past Attempts at Prosthetic Retinas http://singularityhub.com/wp-content/uploads/2010/06/artificial-cornea-prototype.jpg http://www.washingtonpost.com/rf/image_606w/2010-2019/WashingtonPost/2013/02/14/Health-Environment-Science/Images/Retinal%20implant.jpg

8. Background • The research for sight restoring polymers is based on the integration of biological electronics with biological substrates. • An organic film of poly(3-hexylthiophene) (P3HT) was tested and found to trigger neuron firing upon illumination. • This leads to experimentation, which may lead to favorable results in restoring degenerate retina. P3HT Model http://www.intechopen.com/books/application-of-solar-energy/thin-film-solar-cells-modeling-obtaining-and-applications

9. Basic Eye Function • Light flows through the cornea (the black spot in the center of your eye) • It then flows through the lens which causes the dispersal of light • This widening of the light band allows for light to strike the retina over the wide range • The retina interprets this light and converts data into electrical current • This electrical current is then carried to the brain through the optic nerve • Then the brain will interpret this electrical data into images Eye Model http://www.starsandseas.com/SAS%20Physiology/Neurology/Sight.htm

10. Retina Specifics • The main focus of these studies were on Retina function • Specifically the biological material used in retinas turns photons into excited electrons • These excited electrons then turn into the electric current as generated before • Each species retina has its own unique qualities • The range of light wavelengths a human can see is due to the specific properties of the retina Retina Model - Discover Magazine http://discovermagazine.com/2011/sep/17-brain-see-said-blind-man-artifical-retina#.UWmXKLXFV8E

11. Photoexcitation The process chemistry behind photo-excitation http://www.meta-synthesis.com/webbook/17_photo/photo.html

12. Biological Options • Biological growth options have proven to be ineffective over time • The biggest problem is rejection from the body • Drugs that can inhibit the body’s rejection measures tend to also inhibit signaling in retinas thus making the implant useless Organ Transplant Rejection Suppression Drugs http://www.kidney.org/atoz/content/immuno_meds.cfm

13. Finding Appropriate Materials • The biggest problem at the time being for retina replacement is finding an appropriate material to use for this process • The cells of the retina is are complicated • Testing is slow because many materials have significant biological side effects • Asbestos is an example of how knowledge of long term side-effects of material exposure will effect a patient Asbestos http://en.wikipedia.org/wiki/Asbestos

14. Polymers used for Solar Cells Many polymers are used for similar purposes in solar cells Solar Panels http://www.f9solar.com/site/solar_cells Solar Cell Roof http://inhabitat.com/breakthrough-in-cheap-solar-power/

15. Polymer Solution • Many studies have attempted to find an inorganic polymer materials to replace these retina cells • Currently the most promising one is a mixture of poly(3-hexylthiophene) and phenyl-C61-butyric-acid-methyl ester • This blend is commonly referred to as P3HT:PCBM Structures of P3HT and PCBM http://www.light.t.u-tokyo.ac.jp/english/photovoltaic/Introduction.html

16. 3 Basic Tests • There are 3 basic tests have been identified as necessary for a successful retinal replacement material • Interface characterization • Photostimulation of Primary Neurons • Photostimulation of retinal explants Photoelectric Testing http://en.academic.ru/dic.nsf/enwiki/11759175

17. Interface Characterization • First test is done to investigate whether illumination of a pure P3HT film is able to locally modify the electric equilibrium at the polymer-electrolyte interface • The film will yield positive results if it responds by generating a stimulus that is able to induce membrane depolarization in neurons • This test helps determine if the most basic needs of a retinal membrane are met Retinal Interface http://openi.nlm.nih.gov/detailedresult.php?img=2258312_417_2007_743_Fig2_HTML&req=4

18. Test 1 Results a, Schematic representation of the stimulation and recording paradigm. A patch-clamp amplifier is used to detect photocurrents generated by light stimulation through a patch pipette positioned in close proximity (<5 µm) to the P3HT surface. b, Photocurrent detected in voltage-clamp mode with light illumination (20 ms, 15 mW mm−2; green bar). The trace represents an average of five consecutive sweeps. c, Photocurrents generated with repetitive light pulses (20 ms, 15 mW mm−2; green bars) at a repetition rate of 2 Hz. A substantial preservation of the photocurrent is observed during the light pulse train. d, Distribution of photocurrent along the P3HT surface and at increasing distances from the polymer surface. The green circle represents the light spot (100 µm, 20 ms, 15 mW mm−2), and the white and red dots represent the points at which the patch pipette was sequentially positioned. The black dot represents the starting position. e, Mean (±s.e.m.) photocurrent along the P3HT surface, normalized to the amplitude of the first response, is shown as a function of distance from the spot centre (n = 6). f, Left: photocurrent detected in voltage-clamp mode upon light illumination at increasing distances from the polymer surface. Right: mean (±s.e.m.) photocurrent intensity, normalized with respect to the amplitude of the first response, as a function of distance from the polymer surface (n = 6).

19. Test 1 Results Summary • The membrane underwent numerous tests where it underwent pulsed illuminations and electrical effects were measured by an electrode underneath the polymer • The material showed durability by having similar results after numerous exposures to light • The material also showed an ability to withstand a large range of light intensity • It also tested well when light was emitted to anywhere on the surface Material Passed Pulsing Laser http://www.nyccosmeticdermatology.com/wp-content/uploads/2013/01/when-to-turn-to-lasers-laser-expert-new-york.jpg

20. Photostimulation of Primary Neurons • Next the experiments wished to determine whether the same results could be applied to excite a neuron or if it simply translated to electrode transport • Because neuron signaling is complicated numerous materials before failed this test Neuron Model http://www.holisticeducator.com/neuron.htm

21. Test 2 Results a, Schematic representation of the stimulation and recording paradigm. Neuronal responses to light illumination (20 ms, 15 mW mm−2) were detected by patch clamp in current-clamp mode. b, Left: activation by a light pulse (green bar) of a representative neuron cultured on a P3HT-coated glass:ITO substrate (black) and of a neuron cultured on a control glass:ITO coverslip (grey). Right: mean (±s.e.m.) latency to the spike peak with respect to light onset, and latency jitter calculated as the standard deviation of spike latencies measured across all recorded neurons (n = 21). c, Neuronal activation at various frequencies with a train of 20 stimuli (indicated by green bars). Inset (red rectangle): the spike or failure responses to 20 Hz stimulation. d, The percentage of successful spikes in the train of 20 pulses was computed over all recorded neurons and reported as a function of the stimulation frequency (n = 12, mean ± s.e.m.).

22. Test 2 Results Summary • They found that a light pulse was able to depolarize neurons and induce them to fire action potentials • There were short peak latencies and a negligible latency jitter which leads to indicate clear signaling • Results were of the same order of magnitude which indicates high efficiency Material Passed Neuron Firing http://www.holisticeducator.com/neuron.htm

23. Photostimulation of Retinal Explants • Final test is to try this membrane on top of an actual retina and see how the body reacts • These tests were done using retinas which were explanted from albino rats • Tested with both healthy (control) retinas and degenerate retinas which were cause by dim-light exposure Albino Rat Testing https://commons.wikimedia.org/wiki/File:Wistar_rat.jpg

24. Test 3 Results a, Top row: MUAs recorded with light stimulation (10 ms, 4 mW mm−2) of a control retina over a glass:ITO substrate (left), a degenerate retina over a glass:ITO substrate (middle) and a degenerate retina over a P3HT-coated glass:ITO substrate (right). Bottom row: normalized post-stimulus time histograms (PSTHs; bin, 25 ms) computed based on all sweeps recorded in single retinas (10 ms, 4 mW mm−2) for the three experimental conditions. Green bars/arrows represent the light stimulus. b, Comparison of mean (±s.e.m.) PSTHs (bin, 25 ms) obtained from control retinas on glass:ITO (black bars, n = 5), degenerate retinas on glass:ITO (open bars, n = 10) and degenerate retinas on P3HT-coated glass:ITO (red bars, n = 10) in response to light illumination (10 ms, 4 mW mm−2; green arrow). Significantly different bins are indicated (Student's t-test, ***P < 0.001).

25. Test 3 Results Continued c, Dose–response analysis of the mean (±s.e.m.) firing rate versus light intensity performed in degenerate retinas over P3HT-coated glass:ITO (red dots, n = 6) or glass:ITO alone (open dots, n = 6). Mean firing rates were calculated in a window of 250 ms after the light pulse. Dashed line: computed maximum permissible radiant power for chronic exposure. Dose–response curves were fitted using a sigmoidal dose–response model. Solid grey lines represent the response threshold (10% of the maximal response), and dotted grey lines represent the average half-maximum effective dose (ED50) calculated from the fitting procedure (12.11 and 120.78 µW mm−2, respectively). Right: representative PSTHs (bin, 25 ms; means ± s.e.m.) obtained in the presence (red) or absence (grey) of P3HT. The green arrow represents the light stimulus.

26. Test 3 Results Summary • Degenerate retinas on glass hardly responded to light intensity • Healthy retinas responded linearly to increasing light intensity • Degenerate retinas on polymer film responded with four times the amplitude compared to the degenerate retinas on glass Material Passed Figure 3 | The photoreceptor layer is replaced in the degenerate retina by the organic polymer. a, Schematic illustrations of the retinal structure (left) and the stimulation/recording interface for degenerate retinas (right).

27. A Polymer-Electrolyte System • The polymer-electrolyte system differentiates itself from previous versions of retinal implants because it acts as a fuel cell, powered by light rather than some external charging mechanism • Figure shows general mechanism of such a system http://tfy.tkk.fi/aes/AES/projects/renew/fuelcell/pem_index.html

28. Material Selection- P3HT • The biocompatibility of P3HT:PCM has been demonstrated in previous experiments • The goal of this experiment is to contrive a viable single-component device • The interfacing of P3HT alone with the retina shows identical results as the two component system http://carbon.physics.ncsu.edu/2010/07/scattering-factors-for-p3ht/

29. Application • An organic polymer will serve to replace the function of the outer retinal layer, but will require the proper function of the inner retinal layer • Some common diseases that can be cured by this application are… http://curiosity.discovery.com/question/how-artificial-retina-work

30. Macular Degeneration • Defined as the deterioration of the macula, at the center of the retina • Causes loss of the center of one’s field of vision • Caused commonly by old age http://www.uniteforsight.org/course/macular.php

31. Stargardt’s Disease • Similar to macular degeneration, although Stargardt’s disease more commonly affects young people, and is inherited • Affects 1 in 10,000 people and symptoms are usually seen (or rather, not seen) by age 20 • As with macular degeneration, it obstructs central vision due to a defect with the central retina http://www.iovs.org/content/46/1/310/F2.expansion

32. RetinisPigmentosa • Also a genetic disorder, affecting 1 in 4000 people • Especially affects night vision, since it usually damages the rods in the eye • Tunnel vision is another common symptom http://www.eyeinstitute.co.nz/the-eye/eye-problems-and-symptoms/tunnel-vision.htm

33. Material Toxicity • As with previous biological attempts at sight restoration, the body must not reject the prosthetic • P3HT is chosen over other polymers because it is not toxic to the body • Further long-term studies should be done to prove that any deteriorative effects will not damage the eye after a long period of use of the prosthetic, and after long exposure to dirt, chemicals, etc. http://www.ubergizmo.com/2013/03/new-artificial-retina-doesnt-need-external-power-source/

34. Visual spectrum • The polymer-aided retina still struggles at certain light intensities, especially those in outdoor environments • The thickness of the polymer can be fine-tuned to adjust visual range • Multiple layers can be added to increase range http://photographycourse.net/low-light-photo-exercise

35. Polymer vs. Silicon Implants • Silicon implants have been researched in the past, but require an external power source • Polymer implants are autonomous, making for a much more convenient experience for the patient http://www.medgadget.com/2005/04/diamond_coating.html

36. Further Studies • Physical properties must be utilized to obtain desired thickness and wettability • Physical tests on P3HT will show its reliability over time http://www.lia.org/blog/2009/10/wettability-characteristics-variation-of-pmma-by-means-of-co2-laser-generated-surface-patterns/

37. Further Studies • With no external power source, the device will rely solely on light for its electrical charge • How long will this be effective in low-light environments, given the small size of the device? http://www.alternative-energy-resources.net/solarenergyfacts.html

38. Further Studies • Differences between human application and lab rat application • Larger scale- wettability of surface • Personal comfort, since the lenses would be permanent, unlike contact lenses http://hplusmagazine.com/2009/11/20/micro-machines-and-opto-electronics-contact-lense/

39. Further Studies • Continue with multilayer approach to achieve greater range in vision • Possible obstacles- bonding of layers, only using one component • Learn from other areas of photonics research- fiberoptics http://blogs.dctc.edu/continuing-education/2012/11/16/tracking-the-need-for-photonics-technicians-in-our-region/

40. References • Ghezzi, Diego. "A Polymer Optoelectronic Interface Restores Light Sensitivity in Blind Rat Retinas." NATURE PHOTONICS (2013): n. pag. Nature.com. 17 Mar. 2013. Web. 27 Mar. 2013. <http://www.nature.com/nphoton/journal/vaop/ncurrent/full/nphoton.2013.34.html>