Abstract
Purpose :
Unlike mammals, zebrafish regenerate neurons in response to retinal damage. Previously, we showed that acute or chronic retinal damage induces an immune response that modulates the proliferative response in zebrafish larvae. Here, we investigated their role during regeneration following acute or chronic damage in the adult retina.
Methods :
We used adult zebrafish with four different injury models as follows: AB wild-type fish following either NMDA-induced acute retinal damage (1) or needle stab (2), chronic cone photoreceptor-specific degeneration in the gold rush (gosh) mutant (3), or chronic rod degeneration in the Tg[XOPS:mCFP] transgenic line (4). Fishes were treated with dexamethasone to inhibit the immune response. The chronic injury models were also challenged by a NMDA-induced acute damage. Immunohistochemistry of cryosections and flat mount preparations were used to monitor the inflammatory and proliferative response.
Results :
NMDA-treated retinas, stabbed retinas, and the gosh chronic degeneration mutant displayed reactive inflammatory cells and Müller glia proliferation in the inner nuclear layer (INL), but Tg[XOPS:mCFP] retinas possessed inflammatory cells, PCNA-positive outer nuclear layer (ONL) cells, but no Müller glia proliferation. Retinas treated with dexamethasone lacked reactive inflammatory cells and possessed fewer PCNA-positive INL cells, except in Tg[XOPS:mCFP] fish, which displayed similar numbers of PCNA-positive ONL cells. The gosh and Tg[XOPS:mCFP] lines responded to an acute NMDA insult with increased numbers of reactive inflammatory cells and Müller glia proliferation, but at different ratios than NMDA-damaged control fish.
Conclusions :
Acute or chronic retinal damage induces a regenerative response accompanied by an immune response, which depending on the injury, is required for the regenerative response. However, the level of inflammation and amount and type of regenerative cells highly differ between acute and chronic damaged retinas. Understanding the differences and analogies of the inflammatory response following acute and chronic retinal injury is an important step to establishing a strategy to repair mammalian tissues.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.