Abstract
Purpose :
Cyclopterus lumpus (lumpfish) is a marine teleost fish species located throughout the North Atlantic that can be easily cultured. Lumpfish rely heavily on a healthy visual system to survive in the wild and find food sources but are highly prone to cataract development. Cataract is the leading cause of blindness worldwide, but preventative measures are lacking, partially due to the lack of natural animal models. Lumpfish develop nuclear cataract both naturally and spontaneously, which makes them an attractive cataract model. The goal is to further characterize lumpfish cataract and assess whether this can be a good model for the study of human nuclear cataract. We predict that similar disease mechanisms are involved in both species.
Methods :
Eyes of live adult cultured lumpfish were imaged by ophthalmoscopy over a one-year period, and cataract severity was assessed using a cataract grading scale. Cultured lumpfish eyes and lenses were collected for expression marker analyses. We further assessed cataract rates and severities in relation to sex and weight. To assess whether human cataract mechanisms were also involved in lumpfish cataractogenesis, levels of cleaved caspase-3 (a biomarker for apoptosis seen in human cataract) were measured in lumpfish lenses via western blotting and immunohistochemistry.
Results :
Cataract was first detected in young adult cultured lumpfish as early as 250 days post-hatch. By the end of the study, 91% of fish had developed cataract. Cataract development did not significantly impact fish weight. Cataract rates and severities were higher in males (n=56) versus females (n=46). Cleaved caspase-3 was highly expressed in lenses with severe cataract, with little to no expression in lenses with no or mild cataract (ANOVA, p<0.0001), as demonstrated via western blotting. Immunohistochemistry revealed that cleaved caspase-3 is expressed in the dysplastic epithelial cells and disorganized fibre cells of the lens (both associated with severe cataract) of lumpfish cataractous lenses.
Conclusions :
Cultured lumpfish have the potential to be a good animal model for the study of nuclear cataract development. Apoptosis is a known mechanism to be involved in cataract development in humans, and we discovered that this process is also involved in lumpfish cataractogenesis.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.