Speaker
Description
The retina, a light-sensitive tissue at the back of the eye, undergoes neurodegeneration and vision loss with age. Progress in understanding these processes, and in developing treatments for age-related retinal diseases, has been limited by the difficulty of studying aged human tissue and the constraints of traditional animal models. The African turquoise killifish, with its short lifespan of approximately 6 months and conserved retinal structure, provides a powerful alternative model. Previous studies have focused on late-adult stages, showing that killifish recapitulate key features of human retinal ageing. However, understanding how neurons and glia deteriorate with age requires first defining how these cells are established during development. Here, we characterize retinogenesis in killifish from embryonic stages using histology, including the multiplexed immunohistochemistry method we adapted called IBEX. Retinal structure and histogenesis were found to be broadly conserved with zebrafish and mammals. Following hatching, killifish undergo accelerated growth during juvenile stages. We analyzed retinal progenitor proliferation and the ciliary marginal zone (CMZ), identifying enhanced proliferation and expanded stem cell niches during this period. Bulk RNA sequencing of juvenile retinas, combined with pharmacological inhibition of Notch and IGF1R signaling, identified conserved candidate genes and pathways driving this accelerated growth. Our further investigation into the proliferative capacity of the killifish retina has shown that, in addition to lifelong proliferation in the CMZ, the outer nuclear layer of the central retina also continues to proliferate throughout life - a phenomenon not previously described in other model organisms. Single-cell RNA sequencing further revealed genes driving this photoreceptor proliferation in the adult retina. These findings open new avenues for retinal regenerative research by enabling direct investigation of photoreceptor proliferation mechanisms. Together, this work provides the first comprehensive characterization of retinal development in killifish, establishing a foundation for studying retinal neurodegeneration and regeneration across the lifespan.
Lay Abstract
Losing vision is a common part of ageing, often caused by damage to the retina - the part of the eye that detects light. Once these cells are lost, they are very hard to replace. This is why many eye diseases remain difficult to treat. To better understand this problem, researchers are turning to an unexpected model: a small fish that lives for only a few months - the African turquoise killifish. Despite its short life, its retina is built much like ours, allowing scientists to study the full life cycle of eye health and ageing in a short time. Instead of focusing only on ageing, this research explores how the retina is built in the first place. By studying early development, scientists can understand what “healthy” looks like before things begin to go wrong. The study revealed something unusual: this fish can keep producing new retinal cells throughout its life, including those needed for vision - photoreceptors. Most animals and humans lose this ability early on. This discovery opens new possibilities. If we understand how these fish regenerate eye cells, we may one day learn to repair damaged retinas and restore vision.
| Lay Title | How fish can help us understand eyes |
|---|---|
| Role | PhD Student |