Proliferative Inner Nuclear Layer Cells may be a cellular source of retinal regeneration in fish

MP FAILLACE AND JI KORENBROT

Fort Lauderdale, Florida

Congreso; ARVO Meeting 2001; 2001

The Association for Research in Vision and Ophtalmology (ARVO)

New neurons continuously differentiate within the otherwise mature retina of teleostfish, both under normal conditions and in response to injury. We investigated the effects ofsurgical injury and intraocular injection of neurotrophic factors on the mitotic rate of proliferativeinner nuclear layer cells (PINC). PINCare continually born in the inner nuclear layerand then migrate to the outer nuclear layer (ONL). Surgical excision of a part of a retinaactivates PINC mitotic activity near and far fromthe lesion. In the injured eye, up-regulationof PINC cells is largest in the dorsonasal sector of the retina, regardless of the site of lesion.Up-regulation extends even to the unlesioned contralateral eye, where it occurs in the samedorsonasal sector. Intraocular injection of ciliary neurotrophic factor mimics the effect ofinjury on PINC in the treated eye but not on the untreated contralateral retina. We searchedfor the expression in PINC of Pax6, a transcription factor linked to retinal progenitor cellsand found that less than 0.5% of all PINC cells express it. Importantly, the number ofPax6-expressing PINC does not change significantly in the retinas subjected to any of theexperimental manipulations tested. Under normal conditions, the default fate of PINC cellsis to migrate to the ONLand, likely, replenish the rod progenitor pool. PINCrespond to injury(both surgical and light-dependent) by increasing their mitotic rate; this increase is longlived, but there are no changes in the expression level of Pax6. PINC probably are aheterogenous cell population that can be specified for ultimate, different purposes: creatingrod precursors, creating founder cells, creating cone precursors. Several fates are recognizednow, but others may also be possible.