What are retinal prostheses and how do they work?

What are retinal prostheses and how do they work?

Different strategies, such as stem cell replacement, gene therapy and pharmaceutical applications are investigated new treatments aiming to prevent or delay irreversible photoreceptor death and thereby prolong useful vision (Sieving et al., 2006; Scholl et al., 2015; Vighi et al., 2018; Samardzija et al., 2020). Within the schemes of vision restoration, electrical stimulation (ES) via retinal implants has been evolved successfully to promote artificial vision in blind patients (Zrenner, 2013).

But do you know what retinal prostheses are and how they work?

                 Figure 1. Locations of retinal prostheses. Image from Ayton et al., 2020.

 

      Figure 2. A) The epiretinal implant.

    B) The subretinal implant. Images from Zrenner, 2013.

They are implantable devices that stimulate the remaining retinal network to artificially generate visual percepts in patients (Humayun et al., 1999). According to their anatomical placement, ES-based retinal prostheses are classified in: epiretinal, subretinal, suprachoroidal and intrascleral (Fig 1). Epiretinal implants (Fig 2A) are placed on the surface of the neurosensory retina, allowing the direct stimulation of ganglion cells and inner retinal neurons. In contrast, subretinal prosthesis (Fig 2B) are localized in the input region of the retina at the level of the degenerated photoreceptors. Suprachoroidal and intrascleral implants are potentially less invasive and more accessible due to their localization between the sclera and the choroid and within a pocket in the sclera, respectively. However, they are distant from the neurosensory retina, requiring higher current to elicit visual percepts, which could lead to a greater current spread.

In the healthy retina, images from visual scenes are projected by the cornea and lens onto the retina in an upside-down manner and is transformed into an electrical image by rods and cones. With retinal prostheses, the image is acquired by a light-sensing element (e.g., external camera mounted on a pair of glasses or microphotodiodes, depending on their type). Then, image processing algorithms extract the meaningful information and transmit them into an implanted stimulator (in case of photodiode arrays, the stimulator is already integrated in the chip). The generated ES is delivered to the retinal electrode array implanted in the retinal space to stimulate the remaining neurons (Shim et al., 2020).

 If you want to find more about the different types of retinal prosthesis and retinal prosthetic systems currently undergoing development and clinical trials, Ayton et al., 2020 published a review on this topic.

 

Bibliography:

  1. Ayton, L. N., Barnes, N., Dagnelie, G., Fujikado, T., Goetz, G., Hornig, R., Jones, B. W., Muqit, M., Rathbun, D. L., Stingl, K., Weiland, J. D., & Petoe, M. A. (2020). An update on retinal prostheses. Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 131(6), 1383–1398. https://doi.org/10.1016/j.clinph.2019.11.029.
  2. Humayun, M. S., de Juan, E., Jr, Weiland, J. D., Dagnelie, G., Katona, S., Greenberg, R., & Suzuki, S. (1999). Pattern electrical stimulation of the human retina. Vision research, 39(15), 2569–2576. https://doi.org/10.1016/s0042-6989(99)00052-8
  3. Samardzija, M., Corna, A., Gomez-Sintes, R. et al. HDAC inhibition ameliorates cone survival in retinitis pigmentosa mice. Cell Death Differ (2020). https://doi.org/10.1038/s41418-020-00653-3.
  4. Scholl, H. P., Moore, A. T., Koenekoop, R. K., Wen, Y., Fishman, G. A., van den Born, L. I., Bittner, A., Bowles, K., Fletcher, E. C., Collison, F. T., Dagnelie, G., Degli Eposti, S., Michaelides, M., Saperstein, D. A., Schuchard, R. A., Barnes, C., Zein, W., Zobor, D., Birch, D. G., Mendola, J. D., … RET IRD 01 Study Group (2015). Safety and Proof-of-Concept Study of Oral QLT091001 in Retinitis Pigmentosa Due to Inherited Deficiencies of Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT). PloS one, 10(12), e0143846. https://doi.org/10.1371/journal.pone.0143846.
  5. Shim, S., Eom, K., Jeong, J., & Kim, S. J. (2020). Retinal Prosthetic Approaches to Enhance Visual Perception for Blind Patients. Micromachines, 11(5), 535. https://doi.org/10.3390/mi11050535.
  6. Sieving, P. A., Caruso, R. C., Tao, W., Coleman, H. R., Thompson, D. J., Fullmer, K. R., & Bush, R. A. (2006). Ciliary neurotrophic factor (CNTF) for human retinal degeneration: phase I trial of CNTF delivered by encapsulated cell intraocular implants. Proceedings of the National Academy of Sciences of the United States of America, 103(10), 3896–3901. https://doi.org/10.1073/pnas.0600236103.
  7. Vighi, E., Trifunović, D., Veiga-Crespo, P., Rentsch, A., Hoffmann, D., Sahaboglu, A., Strasser, T., Kulkarni, M., Bertolotti, E., van den Heuvel, A., Peters, T., Reijerkerk, A., Euler, T., Ueffing, M., Schwede, F., Genieser, H. G., Gaillard, P., Marigo, V., Ekström, P., & Paquet-Durand, F. (2018). Combination of cGMP analogue and drug delivery system provides functional protection in hereditary retinal degeneration. Proceedings of the National Academy of Sciences of the United States of America, 115(13), E2997–E3006. https://doi.org/10.1073/pnas.1718792115.
  8. Zrenner E. (2013). Fighting blindness with microelectronics. Science translational medicine, 5(210), 210ps16. https://doi.org/10.1126/scitranslmed.3007399.

 

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