To reduce the extensive scarring, we performed a partial optic nerve transection in young adults, leaving a portion of the nerve uninjured. This approach indeed limited scar formation, and it allowed regenerating axons to reach the brain and reinnervate their targets. ✅

Why does this happen? 🔎 A gliofibrotic scar forms at the injury site, an injury response typically associated with mammals. So the axons keep growing, but they physically and chemically can’t overcome the barrier. The result: permanent vision loss.

Even more intriguing: the retinal ganglion cells in killifish retain their intrinsic growth potential. 🧐 However, instead of navigating towards the brain, they misdirect and loop within the retina (yellow arrowheads).

Adult killifish — both young and old — fail to reinnervate their brain target after complete optic nerve transection. 🐠🧠👁️ This is surprising, as most teleost fish are able to fully restore neural circuitry and regain visual function after this type of injury.

All these data were generated by an updated version of RGCode, RGCode2. An automated cell counting platform able to reliable count murine, zebrafish and killifish retinal ganglion cells using RBPMS and Rbpms2 as marker! RGCode2 is publicly available gitlab.com/NCDRlab/rgcode2

Killifish, an aging model shown to lose its regenerative capacity with age, displays a unique biphasic RGC loss profile. Both young adult and old killifish present with a similar degree of RGC loss during the first wave. Old fish, however, lose more RGCs during the second wave.

After optic nerve crush (ONC), mice lose ~80% of their RGC by 14 days post injury (dpi). In contract, zebrafish retain nearly all RGC during the first two weeks, before presenting with late RGC degeneration (~13%) by 21dpi.

Comparing mice, zebrafish and killifish, we were able to determine the differences in retinal ganglion cell (RGC) density between species. Fish species of an equivalent life stage have a five-fold higher density compared to mice. With age, RGC density decreases in killifish.

Killifish, an aging model shown to lose its regenerative capacity with age, displays a unique biphasic RGC loss profile. Both young adult and old killifish present with a similar degree of RGC loss during the first wave. Old fish, however, lose more RGCs during the second wave.

After optic nerve crush (ONC), mice lose ~80% of their RGC by 14 days post injury (dpi). In contract, zebrafish retain nearly all RGC during the first two weeks, before presenting with late RGC degeneration (~13%) by 21dpi.

Comparing mice, zebrafish and killifish, we were able to determine the differences in retinal ganglion cell (RGC) density between species. Fish species of an equivalent life stage have a five fold higher density compared to mice. With age, RGC density decreases in killifish.

Single-cell RNA-sequencing delineates the cellular heterogeneity of the killifish retina, identifying all retinal cell types.

Bulk RNA-seq shows a clear age-related shift in the killifish retinal transcriptome.