A new animal model will facilitate the study and development of gene therapies in retinal diseases.
Reviewed by Elif Ozgecan Sahin, MS. This content originally appeared on our sister site, Modern Retina.
A major cause of visual impairment and blindness is retinal degenerative disease resulting from genetic mutations that affect retinal pigment epithelium (RPE) and retina. Studying these genetic mutations, with the end goal of treating them, will be made easier with the development of a new animal model for gene therapy.
Photoreceptors progressively apoptose with hypoxia and metabolic changes develop in the retina. These dead photoreceptors activate microglial cells that can alter their location in the retinal tissue, resulting in further photoreceptor degeneration due to the release of proinflammatory cytokines.
Elif Ozgecan Sahin, MS, under the supervision of Salih Sanlioglu, VMD, PhD, from the Department of Gene and Cell Therapy at Akdeniz University in Antalya, Turkey, explained during a presentation at the American Society of Gene & Cell Therapy 2021 Virtual Annual Meeting that because the type of mutation present controls the photoreceptor degeneration, the pathologies seen in the hereditary retinal dystrophies are similar.
Realization of this similarity sparked the need for development of a new animal model of retinal degeneration that exhibits the pathologies seen in all the inherited retinal dystrophies, she said.
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The investigators then set out to create an in vitro retinal degeneration model by treating ARPE-19 cells with cobalt chloride (CoCl2), an agent that triggers hypoxia. Western blot analysis confirmed the hypoxia and degeneration using antibodies against HIF1A. The next step then was generation of hypoxia in vivo by injecting CoCl2 intravitreally into Wistar rats.
Sahin pointed out that evaluation of their efforts via hematoxylin and eosin staining and TUNEL assay results “indicated that progressive retinal degeneration initiated in the outer segment of the photoreceptors and then further extended into the other retinal layers over time.” Changes began to be observed in the first 48 hours following the CoCl2 injection.
She also reported that the CoCl2 activated microglia cells that were visualized by CD68 immune staining; the cells were scattered throughout the retinal layers.
“All these results indicate that this chemical agent–induced animal model can be used successfully for gene therapy studies targeting retinal degeneration,” she concluded.