The influence of subretinal injection pressure on the microstructure of the monkey retina

Kosuke Takahashi, Yuki Morizane, Toshio Hisatomi, Takashi Tachibana, Shuhei Kimura, Mio Morizane Hosokawa, Yusuke Shiode, Masayuki Hirano, Shinichiro Doi, Shinji Toshima, Ryoichi Araki, Hiroshi Matsumae, Yuki Kanzaki, Mika Hosogi, Atsushi Yoshida, Koh Hei Sonoda, Fumio Shiraga

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Purpose To investigate the influence of subretinal injection pressure on the microstructure of the retina in a monkey model. Methods After vitrectomy, balanced salt solution was injected subretinally into one eye each of four cynomolgus monkeys while controlling the injection pressure. Initially, a pressure of 2 psi was used, and this was gradually increased to determine the minimum required pressure. Subsequent injections were performed at two pressures: minimum (n = 13) and high (n = 6). To compare the influence of these injection pressures on retinal structure, optical coherence tomography (OCT) was performed before surgery and every week afterwards. The monkeys were euthanized and their eyes were enucleated at 1 or 6 weeks after the injections. The eyes were processed for light microscopy and transmission electron microscopy (TEM) as well as for TdT-mediated dUTP nick end labeling. Results The minimum pressure required to perform subretinal injection was 6 psi. After injection at this pressure, both OCT and microscopy showed that the retinal structure was well-preserved throughout the experimental period at all injection sites. Conversely, after injection at high pressure (20 psi) OCT images at all injection sites showed disruption of the ellipsoid zone (EZ) after 1 week. Microscopy indicated damage to the photoreceptor outer segment (OS) and stratification of the retinal pigment epithelium (RPE). After 6 weeks, OCT demonstrated that the EZ had become continuous and TEM confirmed that the OS and RPE had recovered. Photoreceptor apoptosis was absent after subretinal injection at both pressures. Conclusions The retinal damage caused by subretinal injection increases depending on pressure, indicating that clinicians should perform subretinal injection at pressures as low as possible to ensure safety.

Original languageEnglish
Article numbere0209996
JournalPloS one
Volume13
Issue number12
DOIs
Publication statusPublished - Dec 2018

Fingerprint

retina
microstructure
Haplorhini
monkeys
Retina
injection
Pressure
Microstructure
Injections
Optical tomography
tomography
Optical Coherence Tomography
Retinal Pigments
Microscopy
injection site
eyes
Retinal Pigment Epithelium
photoreceptors
Transmission Electron Microscopy
transmission electron microscopy

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Takahashi, K., Morizane, Y., Hisatomi, T., Tachibana, T., Kimura, S., Hosokawa, M. M., ... Shiraga, F. (2018). The influence of subretinal injection pressure on the microstructure of the monkey retina. PloS one, 13(12), [e0209996]. https://doi.org/10.1371/journal.pone.0209996

The influence of subretinal injection pressure on the microstructure of the monkey retina. / Takahashi, Kosuke; Morizane, Yuki; Hisatomi, Toshio; Tachibana, Takashi; Kimura, Shuhei; Hosokawa, Mio Morizane; Shiode, Yusuke; Hirano, Masayuki; Doi, Shinichiro; Toshima, Shinji; Araki, Ryoichi; Matsumae, Hiroshi; Kanzaki, Yuki; Hosogi, Mika; Yoshida, Atsushi; Sonoda, Koh Hei; Shiraga, Fumio.

In: PloS one, Vol. 13, No. 12, e0209996, 12.2018.

Research output: Contribution to journalArticle

Takahashi, K, Morizane, Y, Hisatomi, T, Tachibana, T, Kimura, S, Hosokawa, MM, Shiode, Y, Hirano, M, Doi, S, Toshima, S, Araki, R, Matsumae, H, Kanzaki, Y, Hosogi, M, Yoshida, A, Sonoda, KH & Shiraga, F 2018, 'The influence of subretinal injection pressure on the microstructure of the monkey retina', PloS one, vol. 13, no. 12, e0209996. https://doi.org/10.1371/journal.pone.0209996
Takahashi K, Morizane Y, Hisatomi T, Tachibana T, Kimura S, Hosokawa MM et al. The influence of subretinal injection pressure on the microstructure of the monkey retina. PloS one. 2018 Dec;13(12). e0209996. https://doi.org/10.1371/journal.pone.0209996
Takahashi, Kosuke ; Morizane, Yuki ; Hisatomi, Toshio ; Tachibana, Takashi ; Kimura, Shuhei ; Hosokawa, Mio Morizane ; Shiode, Yusuke ; Hirano, Masayuki ; Doi, Shinichiro ; Toshima, Shinji ; Araki, Ryoichi ; Matsumae, Hiroshi ; Kanzaki, Yuki ; Hosogi, Mika ; Yoshida, Atsushi ; Sonoda, Koh Hei ; Shiraga, Fumio. / The influence of subretinal injection pressure on the microstructure of the monkey retina. In: PloS one. 2018 ; Vol. 13, No. 12.
@article{f96ca8b0567c4add97619e41339dd287,
title = "The influence of subretinal injection pressure on the microstructure of the monkey retina",
abstract = "Purpose To investigate the influence of subretinal injection pressure on the microstructure of the retina in a monkey model. Methods After vitrectomy, balanced salt solution was injected subretinally into one eye each of four cynomolgus monkeys while controlling the injection pressure. Initially, a pressure of 2 psi was used, and this was gradually increased to determine the minimum required pressure. Subsequent injections were performed at two pressures: minimum (n = 13) and high (n = 6). To compare the influence of these injection pressures on retinal structure, optical coherence tomography (OCT) was performed before surgery and every week afterwards. The monkeys were euthanized and their eyes were enucleated at 1 or 6 weeks after the injections. The eyes were processed for light microscopy and transmission electron microscopy (TEM) as well as for TdT-mediated dUTP nick end labeling. Results The minimum pressure required to perform subretinal injection was 6 psi. After injection at this pressure, both OCT and microscopy showed that the retinal structure was well-preserved throughout the experimental period at all injection sites. Conversely, after injection at high pressure (20 psi) OCT images at all injection sites showed disruption of the ellipsoid zone (EZ) after 1 week. Microscopy indicated damage to the photoreceptor outer segment (OS) and stratification of the retinal pigment epithelium (RPE). After 6 weeks, OCT demonstrated that the EZ had become continuous and TEM confirmed that the OS and RPE had recovered. Photoreceptor apoptosis was absent after subretinal injection at both pressures. Conclusions The retinal damage caused by subretinal injection increases depending on pressure, indicating that clinicians should perform subretinal injection at pressures as low as possible to ensure safety.",
author = "Kosuke Takahashi and Yuki Morizane and Toshio Hisatomi and Takashi Tachibana and Shuhei Kimura and Hosokawa, {Mio Morizane} and Yusuke Shiode and Masayuki Hirano and Shinichiro Doi and Shinji Toshima and Ryoichi Araki and Hiroshi Matsumae and Yuki Kanzaki and Mika Hosogi and Atsushi Yoshida and Sonoda, {Koh Hei} and Fumio Shiraga",
year = "2018",
month = "12",
doi = "10.1371/journal.pone.0209996",
language = "English",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - The influence of subretinal injection pressure on the microstructure of the monkey retina

AU - Takahashi, Kosuke

AU - Morizane, Yuki

AU - Hisatomi, Toshio

AU - Tachibana, Takashi

AU - Kimura, Shuhei

AU - Hosokawa, Mio Morizane

AU - Shiode, Yusuke

AU - Hirano, Masayuki

AU - Doi, Shinichiro

AU - Toshima, Shinji

AU - Araki, Ryoichi

AU - Matsumae, Hiroshi

AU - Kanzaki, Yuki

AU - Hosogi, Mika

AU - Yoshida, Atsushi

AU - Sonoda, Koh Hei

AU - Shiraga, Fumio

PY - 2018/12

Y1 - 2018/12

N2 - Purpose To investigate the influence of subretinal injection pressure on the microstructure of the retina in a monkey model. Methods After vitrectomy, balanced salt solution was injected subretinally into one eye each of four cynomolgus monkeys while controlling the injection pressure. Initially, a pressure of 2 psi was used, and this was gradually increased to determine the minimum required pressure. Subsequent injections were performed at two pressures: minimum (n = 13) and high (n = 6). To compare the influence of these injection pressures on retinal structure, optical coherence tomography (OCT) was performed before surgery and every week afterwards. The monkeys were euthanized and their eyes were enucleated at 1 or 6 weeks after the injections. The eyes were processed for light microscopy and transmission electron microscopy (TEM) as well as for TdT-mediated dUTP nick end labeling. Results The minimum pressure required to perform subretinal injection was 6 psi. After injection at this pressure, both OCT and microscopy showed that the retinal structure was well-preserved throughout the experimental period at all injection sites. Conversely, after injection at high pressure (20 psi) OCT images at all injection sites showed disruption of the ellipsoid zone (EZ) after 1 week. Microscopy indicated damage to the photoreceptor outer segment (OS) and stratification of the retinal pigment epithelium (RPE). After 6 weeks, OCT demonstrated that the EZ had become continuous and TEM confirmed that the OS and RPE had recovered. Photoreceptor apoptosis was absent after subretinal injection at both pressures. Conclusions The retinal damage caused by subretinal injection increases depending on pressure, indicating that clinicians should perform subretinal injection at pressures as low as possible to ensure safety.

AB - Purpose To investigate the influence of subretinal injection pressure on the microstructure of the retina in a monkey model. Methods After vitrectomy, balanced salt solution was injected subretinally into one eye each of four cynomolgus monkeys while controlling the injection pressure. Initially, a pressure of 2 psi was used, and this was gradually increased to determine the minimum required pressure. Subsequent injections were performed at two pressures: minimum (n = 13) and high (n = 6). To compare the influence of these injection pressures on retinal structure, optical coherence tomography (OCT) was performed before surgery and every week afterwards. The monkeys were euthanized and their eyes were enucleated at 1 or 6 weeks after the injections. The eyes were processed for light microscopy and transmission electron microscopy (TEM) as well as for TdT-mediated dUTP nick end labeling. Results The minimum pressure required to perform subretinal injection was 6 psi. After injection at this pressure, both OCT and microscopy showed that the retinal structure was well-preserved throughout the experimental period at all injection sites. Conversely, after injection at high pressure (20 psi) OCT images at all injection sites showed disruption of the ellipsoid zone (EZ) after 1 week. Microscopy indicated damage to the photoreceptor outer segment (OS) and stratification of the retinal pigment epithelium (RPE). After 6 weeks, OCT demonstrated that the EZ had become continuous and TEM confirmed that the OS and RPE had recovered. Photoreceptor apoptosis was absent after subretinal injection at both pressures. Conclusions The retinal damage caused by subretinal injection increases depending on pressure, indicating that clinicians should perform subretinal injection at pressures as low as possible to ensure safety.

UR - http://www.scopus.com/inward/record.url?scp=85059256543&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85059256543&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0209996

DO - 10.1371/journal.pone.0209996

M3 - Article

C2 - 30596769

AN - SCOPUS:85059256543

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e0209996

ER -