Reciprocal Changes in Factor XIII and Retinal Transglutaminase Expressions in the Fish Retina During Optic Nerve Regeneration

Abstract

Unlike mammals, fish retinal ganglion cells have the capacity to repair their axons even after optic nerve transection. In the process of fish optic nerve regeneration, a large number of genes have been described as regeneration-associated molecules. Using molecular cloning techniques, we identified two types of cDNA clones belonging to the transglutaminase (TG) family which were upregulation genes; one is cellular factor XIII (cFXIII) and the other is a tissue type TG named retinal transglutaminase (TG_R). cFXIII mRNA started to increase in the retinal ganglion cells at 1–2 days, peaked at 5–7 days, and returned to the control level by 20 days post optic nerve injury. In contrast, TG_R mRNA started to increase at day 5–10, peaked at day 20, and then gradually decreased by day 40 after nerve injury. To elucidate the molecular involvement of these TGs in optic nerve regeneration, we studied the effects of recombinant TG_R protein or overexpression of cFXIII using a retinal explant culture system. cFXIII effectively induced neurite outgrowth only from naïve (intact) retinas. In contrast, the TG_R protein significantly enhanced neurite outgrowth only from primed retinas, in which the optic nerve had been crushed 5–7 days previously. These reciprocal expressions of cFXIII and TG_R suggest that these two types of TGs are important for the neurite sprouting and axonal elongation processes, respectively, during optic nerve regeneration processes.