Structural changes in the retina after implantation of subretinal three-dimensional implants in mini pigs

Que Anh Vu; Hee Won Seo; Kwang-Eon Choi; Namju Kim; Yoo Na Kang; Jaemeun Lee; Sun-Hyun Park; Jee Taek Kim; Sohee Kim; Seong-Woo Kim

doi:10.3389/fnins.2022.1010445

Structural changes in the retina after implantation of subretinal three-dimensional implants in mini pigs

Front Neurosci. 2022 Sep 30:16:1010445. doi: 10.3389/fnins.2022.1010445. eCollection 2022.

Authors

Que Anh Vu^{1

2}, Hee Won Seo³, Kwang-Eon Choi¹, Namju Kim³, Yoo Na Kang⁴, Jaemeun Lee⁵, Sun-Hyun Park⁵, Jee Taek Kim⁶, Sohee Kim³, Seong-Woo Kim¹

Affiliations

¹ Department of Ophthalmology, Korea University School of Medicine, Seoul, South Korea.
² Department of Ophthalmology, Hanoi Medical University, Hanoi, Vietnam.
³ Department of Robotics and Mechatronics Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, South Korea.
⁴ Department of Medical Assistant Robot, Korea Institute of Machinery and Materials (KIMM), Daegu, South Korea.
⁵ R&D Center for Advanced Pharmaceuticals and Evaluation, Korea Institute of Toxicology, Daejeon, South Korea.
⁶ Department of Ophthalmology, Chung-Ang University College of Medicine, Seoul, South Korea.

Abstract

The retinal structural changes after subretinal implantation of three-dimensional (3D) microelectrodes were investigated in a mini pig. Three types of electrode were implanted into the subretinal spaces of nine mini pigs: 75-μm-high 3D electrodes on a 200-μm-thick right-angled polydimethylsiloxane (PDMS) substrate (group 1); a 140-μm-thick sloped PDMS substrate without electrodes (group 2); and a 140-μm-thick sloped PDMS substrate with 20-μm-high 3D electrodes (group 3). One mini pig was used as a control. Spectral domain-optical coherence tomography (SD-OCT) images were obtained at baseline and 2, 6, and 12 weeks post-surgery. Retinal specimens were immunostained using a tissue-clearing method 3 months post-implantation. The 75-μm-high 3D electrodes progressively penetrated the inner nuclear layer (INL) and touched the inner plexiform layer (IPL) 2 weeks post-surgery. At 6 weeks post-operatively, the electrodes were in contact with the nerve-fiber layer, accompanied by a severe fibrous reaction. In the other groups, the implants remained in place without subretinal migration. Immunostaining showed that retinal ganglion and bipolar cells were preserved without fibrosis over the retinal implants in groups 2 and 3 during the 12-week implantation period. In summary, SD-OCT and immunohistology results showed differences in the extent of reactions, such as fibrosis over the implants and penetration of the electrodes into the inner retinal layer depending on different types of electrodes. A sloped substrate performed better than a right-angled substrate in terms of retinal preservation over the implanted electrodes. The 20-μm-high electrodes showed better structural compatibility than the 75-μm-high 3D electrodes. There was no significant difference between the results of sloped implants without electrodes and 20-μm-high 3D electrodes, indicating that the latter had no adverse effects on retinal tissue.

Keywords: implant design; retinal prosthesis; structural retinal change; subretinal implant; three-dimensional microelectrodes.