Cellular remodelling of the inner retina and the retinal ganglion cells in experimental retinal detachment

Abstract

AbstractPurpose: Anatomical surgical outcomes for the treatment of retinal detachment (RD) are outstanding; however, only 50% of the patients with a detached macula regain 5/10 or better vision. Thus, to preserve or restore visual function in RD, several gaps in our understanding of the pathophysiology of the disease need to be bridged. Therefore, the purpose of the current study, was to investigate the anatomical/morphological changes of retinal interneurons and retinal ganglion cells (RGCs) in an experimental model of RD.Methods: Experimental RD was induced in C57BL6/J mice by a subretinal injection of 1% sodium hyaluronate. Following RD, mice were euthanized at 1‐, 3‐, 7‐, 30‐ and 90‐days post‐surgery and eyes or retinas were isolated and proceed for sectioning or retinal whole mounts respectively. Immunofluorescence and electron microscopy studies were performed against protein kinase C alpha (PKC‐α) to target rod bipolar cells, calretinin and calbindin D to target horizontal cells and brain‐specific homeobox/POU domain protein 3A (Brn3a) and neuron‐specific class III beta‐tubulin (β‐tubulin III) to target RGCs.Results: Three days post‐RD, PKC‐α+ neurons (rod bipolar cells) began to migrate towards the outer nuclear layer (ONL), while 30 days post‐RD they had significantly migrated towards the ONL and displayed irregular distribution of their cell bodies in the inner nuclear layer. Similarly, processes of horizontal cells also migrated towards the ONL, 7 days post‐RD and became more invasive and disoriented after longer‐term detachment (30 days post‐surgery). Moreover, there was a significant increase in the intensity of calbindin D, 30‐days post‐RD. Brn3a/β‐tubulin ΙΙΙ+ RGCs were significantly fewer 30‐ and 90‐days post RD. All retinal neurons that were examined, did not show any noteworthy differences 1 day post RD.Conclusions: RD resulted in significant anatomical changes in both rod bipolar and horizontal neurons of the retina along with a notable reduction of RGCs. The cellular response of the inner retina and the RGCs of the detached retina might play an important role in the imperfect visual score of an anatomical successful surgical reattachment.