Photoelectric Responsive Polymer Microarray As Bionic Artificial Retina To Restore Vision

For modern biomedicine,it is a great challenge to construct flexible artificial retina that has high spatial resolution to achieve accurate optic nerve correspondence.Vision is the most important sense of human beings.The retina plays a key role in the formation of visual images.When visible light is irradiated on the retina,the photoreceptor cells can convert the incoming electromagnetic radiation into electrical signals.Then,the optic nerve pathway sends the electrical information to the visual centers to form vision,which then forms the vivid images in our mind.There are about 30 million blind people in the world.If artificial photoreceptors are used instead of the natural retina to generate electrical impulses to the optic nerve,the visual function can be restored.The traditional method to restore vision of the blind is to implant metal electrodes that can conduct external electrical signals to stimulate the remaining optic nerve.The implanted electrodes with electronic accessories are incompatible with biological tissues,increases the difficulty of surgery,and brings economic burden to the visually impaired patients.The natural retina has hundreds of millions of nerve cells connected with each other in a complicated way.In order to achieve high resolution,the artificial retina should have the same optical sensing and nerve signal transduction units as the natural photoreceptor cells.In this thesis,we design an artificial retina having microarray of photoelectric responsive polymer.It has photoconductive units with size smaller than that of nerve cells.Photoreceptor array with periodic sensing units of pyramidal geometry is fabricated by microscale processing technology.The semiconductor heterojunction of conjugated polymer and PCBM in each sensing unit realizes the conversion of optical signals into electric signals based on the principle of photoinduced electric charge transfer.We specifically label the conjugated polymers with folate molecules,which play an important role in eye development,and high expression of folate receptors is found in the nerve cells.In such way,artificial retina achieves enhanced stimulation of the nerve through the receptor recognition on the cell membrane.We implant the artificial retina into the eyes of blind rats through external surgery.The electrophysiological analysis shows that the photosensitive function of the blind rats is recovered in the presence of the artificial retina.Our work shows that photoelectric responsive materials can effectively activate the optic nerves by light,providing a new way to artificial retina.The main research results of this thesis are summarized as follows:1.We use polythiophene derivatives as the main functional materials to construct the photoelectric conversion device.The device has many bionic visual functions.To meet the requirement of stimulation and accurate communication with nerve cells,we not only use the micro-processing technology to fabricate the device with surface morphology of periodic microarray,but also modify its with folic acid,so as to enhance the stimulation effect of artificial retina on nerves.2.We construct the photoelectric conversion device by using semiconductor heterojunction of electron donor and acceptor.The electric signal converted from blue light can reach hundreds of millivolts,and satisfy the demand of neural stimulation.The timely response to high-frequency flashing light also verifies the high sensitivity of the device.By using solution-casting technique that transfers the microarray pattern of the template to the artificial retina,we achieve photoreceptor units as small as three microns.Multiple artificial photoreceptors can contact with a single nerve cell at the same time,which facilitates the communication between artificial retina and neurons.3.We culture the nerve cells with the artificial retina.Visible light is applied to the artificial retina in the hope that it will convert light into electrical signals to stimulate nerve cells.Confocal laser scanning microscope is used to observe the luminescence intensity of intracellular calcium ion fluorescent probe.It verifies that the neurons communicate with the surrounding environment in response to the photoelectric stimulation brought about by the artificial retina.When shrinking the light-spot to individual nerve cells,the cells exposed to the light experience a significant influx of calcium ions.Thus,the single cell can be activated by a single pixel of the artificial retina,confirming its high spatial resolution.4.We detect the expression level of synaptophysin to prove that the artificial retina does affect the physiological activities of the nerve cells.The synaptic structure of the retinal neuronal layer determines the visual function,and the synaptophysin is an important factor in the process of nerve signal transmission.The expression of the synaptophysin in the nerve cells cultured with the artificial retina is significantly up-regulated,indicating that the artificial retina has the potential to regulate nerve cells.5.We implant the artificial retinas into the subretinal space of blind rats.Optical imaging of the fundus verifies its biosafety and long-term stability.Both visual evoked potential(VEP)and pupil to light reflex(PLR)signal enhancement demonstrate that the artificial retinas achieves nerve stimulation and restoration of visual system function of the blind rats.Our research provides a new insight into the high-resolution artificial vision system and brain-computer interface.