Abstract
Abstract: :
Purpose: To examine the changes in synaptic connectivity between photoreceptors and their target cells immunocytochemically and to correlate these changes with retinal function using the electroretinogram (ERG). Methods: 15 dystrophics RCS rats (rdy+p+) at P21, P30, P60, P90 and P120 and 3 congenic non–dystrophic RCS rats (rdy–p+) at P30 were studied anatomically and with ERG recordings. Results: Staining with bassoon and synaptophysin (presynaptic markers) and mGluR6 (postsynaptic marker for ON bipolar dendrites) was already impaired at P21 and progressively lost with infrequent pairing of pre– and post–synaptic elements at P60. Staining became increasingly patchy up to P90, and by P120 was sparse, irregular and devoid of any pairing associations. Sprouting of bipolars and horizontal cells into the debris zone was clearly seen at P90, but disappeared at older ages, starting from the central area towards the periphery as the debris zone resorbed. Sprouting of horizontal cell processes into the IPL was seen at P90 to P120. Rod–driven ERG responses were already reduced by P21 and lost at P60. Cone–driven responses were normal up to P30. First signs of dysfunction were seen at P60, but responses could still be recorded at P120, although with reduced amplitude. Conclusions: The synaptic markers associated with photoreceptors and the processes of bipolar and horizontal cells show abnormalities prior to significant photoreceptor loss. Progression of these changes results in the sprouting of bipolar and horizontal cell dendrites into the debris zone followed by their retraction upon resorbtion of this zone at later degenerative stages. These changes are paralleled with the deterioration of specific aspects of ERG responsiveness with age.
Keywords: retinal degenerations: cell biology • photoreceptors • electroretinography: non-clinical