Müller Glia Cell Activation in a Laser-induced Retinal Degeneration and Regeneration Model in Zebrafish

Abstract

A fascinating difference between teleost and mammals is the lifelong potential of the teleost retina for retinal neurogenesis and regeneration after severe damage. Investigating the regeneration pathways in zebrafish might bring new insights to develop innovative strategies for the treatment of retinal degenerative diseases in mammals. Herein, we focused on the induction of a focal lesion to the outer retina in adult zebrafish by means of a 532 nm diode laser. A localized injury allows investigating biological processes that take place during retinal degeneration and regeneration directly at the area of damage. Using non-invasive optical coherence tomography (OCT), we were able to define the location of the damaged area and monitor subsequent regeneration in vivo. Indeed, OCT imaging produces high-resolution, cross-sectional images of the zebrafish retina, providing information which was previously only available with histological analyses. In order to confirm the data from real-time OCT, histological sections were performed and regenerative response after the induction of the retinal injury was investigated by immunohistochemistry.

Noninvasive Imaging of Cone Ablation and Regeneration in Zebrafish

“…To our knowledge, several other studies use OCT to evaluate retinal damage in zebrafish. 26,30,[45][46][47][48] The study by Bailey et al 26 uses pan-retinal models of damage (retinal ablation with light and ouabain injection) and analyzes retinal changes from B-scans. Weber et al 30 uses both diffuse light and focused light approaches to ablate the retina.…”

Diverse Signaling by TGFβ Isoforms in Response to Focal Injury is Associated with Either Retinal Regeneration or Reactive Gliosis

“…In zebrafish, after anesthesia with 0.16 mg/mL ethyl 3-aminobenzoate methanesulfonate salt (Tricaine; Sigma-Aldrich, Buchs, Switzerland) dissolved in the tank water, 1–2 drops of 2% hydroxypropyl methylcellulose (Methocel, OmniVision AG, Neuhausen, Switzerland) were topically applied to the cornea. A diode laser with a wavelength of 532 nm (Visulas 532 s, Carl Zeiss Meditec AG, Oberkochen, Germany) was used to create retinal lesions at the region of the posterior pole around the optic nerve (Conedera et al 2017 ). These were confined to the ONL (outer nuclear layer) and surrounded by healthy tissue.…”

Model systems for regeneration: zebrafish

“…Subsequently, the transient scar tissue regresses and is replaced by new cardiac tissue (Gonzalez-Rosa et al, 2012). As well as low temperatures, cell death can be induced by exposure to high temperatures, either using a heated metal rod (Raymond et al, 2006) or by applying a light source in a determined region (Conedera et al, 2017;Vihtelic and Hyde, 2000).…”