Establishment and characterization of a unilateral UV-induced photoreceptor degeneration model in the C57Bl/6J mouse and chinchilla bastard rabbit

• Etablierung und Charakterisierung eines unilateralen UV-induzierten Photorezeptordegenerationsmodells in der C57Bl6/J Maus und im Chinchilla Bastard Kaninchen

van der Meer, Anna-Marina; Kampa, Björn Michael (Thesis advisor); Walter, Peter Markus (Thesis advisor); Müller, Frank (Thesis advisor)

Aachen (2019, 2020)
Dissertation / PhD Thesis

Dissertation, RWTH Aachen University, 2019

Abstract

In order to test retinal implants and establish surgical procedures for patients suffering from retinal degenerative diseases, e.g. retinitis pigmentosa (RP), large-eye animal models emulating the characteristics of RP are required. Although the retinal degeneration 10 (rd10) mouse - a genetic model for RP - has been thoroughly investigated in the past, it does not provide a sufficiently large eye to further develop retinal implants. For that purpose, the rabbit is the ideal model organism, as the eye is in size comparable to the human eye and the animals are fairly easy to keep and handle. Although a genetic model for RP already exists in the rabbit (TgP347L), an inducible/acute model for retinal degeneration is advantageous: The onset of the degeneration can be externally triggered, the degeneration process is faster and the untreated eye can be used as an internal control. In order to establish such an induced model for retinal degeneration, left eyes of C57Bl/6J mice were irradiated with a UV LED array at 370 nm, as a first step in this project. A dose escalation study was performed in the mouse, followed by a characterization study that allowed the comparison to the well established rd10 mouse model. The short and long term effects on the retina were evaluated. Slit lamp examinations, full-field electroretinography (ffERG), spectral-domain optical coherence tomography (sd-OCT), macroscopy, histology and multielectrode array (MEA) recordings were deployed to find a suitable dosage and to assess the impact of the UV irradiation on the eye. During the characterization study additional MEA recordings and immunohistochemical stainings were used to get a more detailed impression of the irradiated retina. The technique of UV irradiation was then used on Chinchilla Bastard rabbits to likewise induce retinal degeneration. Here, slit lamp examinations, ffERG, multifocal electroretinography (mfERG), sd-OCT, macroscopy and histology was utilized to find a suitable dosage and to document the effect of UV radiation on the eye. The irradiation of the eye with UV light leads to a reproducible photoreceptor degeneration in the mouse with a strong resemblance to the rd10 mouse model, whereas in the rabbit the most severe damage is inflicted on the cornea, with only mild effects on the retina.

Institutions

• Department of Biology [160000]
• Department of Molecular and Systemic Neurophysiology [162320]